physio exam 2

optogenetics

* light and genetics
* new tool for correlating neuronal circuit activity with behavior
* controlling neuron activity by using light and genetic engineering
* mouse infected with virus = light sensitive channels that produce an AP without change in voltage
* when exposed to blue light = AP, channelrhodopsins

name of student who worked with him

Scott Varga

optogenetics in Drosophilia larva

* genetically modified to have light sensing channels
* exposed to blue light 470nm, curled up when exposed
* test locomotor symptoms to look for improvement

transmission of information within a single neuron: flow info, morpho features, cable properties of axons, myelin, passive propagation, Rm Rl

* ion channels > ionic currents > AP
* input @ dendrites, cell body - integration, AP generated at axon hillock, axon propagates AP to terminals


* morphological feature: long & thin processes
* cable properties of axons: decays with distance


1. cytoplasmic R to electrical signals
2. leaking through plasma membrane - insulation = bad
* myelin = mostly lipid, insulates electrical flow
* passive propagation: current
* higher membrane resistance = insulation better
* smaller diameter axon = high resistance, longitudinal resistance (Rl)
* membrane resistance = Rm = resistance to current flow out across membrane?

passive spread of electrical signals: lambda

* lambda = length constant, represents distance at which decaying voltage change is 37% of its value at the origin
* lambda = sqrt(Rm/Rl)
* high Rm, Low Rl = large lambda
* current decreases = expo decay
* Vx=Vo\* e^-x/lambda
* lambda = Vo @37%
* expo decrease in membrane current

speed of propagation depends on 3

1) temperature

2) greater lambda length constant

3) # channels

how to increase lambda 2

1) increase axon size: Rl will decrease because less resistance

2) increase myelination: increases Rm

saltatory conductance

AP jumping propagation because of myelination, cannot stop in myelin, Na channels are only expressed at node of ranvier, so AP jumps around, AP propagation is much faster in mammals 

_ axon = __ resistance = _ flow

_ lambda = __ propagation speed

bigger axon = less resistance = greater flow

what happens if axon too long with no nodes of ranvier

AP cannot travel to terminals, current decays too fast

nodes of ranvier VG Na and K channels help continue AP → more channels = increases speed of propagation

propagation of a nerve impulse AP - 2

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1) local circuits - AP propagation

2) unidirectional - excitability Na channels

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* VG lets Na+ into cell, inside cell = negative, +/- charges attracted to each other = local current, ions are moving bidirectionally
* AP needs to move in one direction
* how AP move in one direction? Na inactivation ends local circuit/ back propagation

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two functions of Na inactivation

1) overexcitation

2) unidirectional direction of AP

velocity of nerve impulse conduction increases with

increasing axon diameter with and without myelination

transmission of information between neurons

stimulus + sensory neuron + CNS/ interneuon + motor neuron + ouput (muscle contraction)

echolocation + bats/moth

echolocation: noctural encounter between moth and bat

bat generates ultrasonic sound

object nearby (moth) reflects sound back to bat

moth is also able to detect ultrasonic sound

moth makes rapid unpredictable movements to confuse the bat and escape

how is sensory information conveyed to the NS - 3 steps

* transduction: convert external stimulus to internal signal (electrical - voltage), interneurons cannot recognize direct external stimulus, must make it so they understand
* amplification: of signal, separate background noise from important signal, DOESN’T always occur
* transmission: signal to CNS where signal is integrated/ processed with other signals

transduction

* requires sensory receptor cell to convert external stimulus to electrical signal
* sensory organs: specialized for reception of particular kinds of stimuli (includes sensory receptor cells)
* sensory systems: sense organs and all of their associated central processing areas (organs, neurons, receptors, etc all)

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sensory receptors (receipt, transduction, amplification) → sensory input → CNS (integration of information) → motor output → effectors (response to signals)

labeled lines principle

*The sensory modality or quality of sensation associated with a stimulus depends solely on which receptor cells are stimulated, rather than on how they are stimulated*.

sensory systems are separate but can work together

labeled lines: sensory neurons → CNS

touch and smell are directly connected

taste, light, and sound require secondary sensory neurons, no direct

classification of sensory receptor cells 4

1) sensory modality: subjective nature of sensory stimulus (good/bad/pretty/ugly/etc)

2) forms of stimulus energy: light, touch, sound, balance, pressure, etc

3) mechanisms of transduction

4) location of the source of the stimulus energy: exteroceptor = external stimuli, interoceptor = internal stimuli

2 kinds of sensory transduction mechanisms

types of sensing

1. ionotropic transduction: direct, faster
* ligand gated channels
2. metabotropic transduction: slower, more amplified, indirect

* G-protein mediated signaling

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mechanoreception + touch

vestibular organs + hearing

chemoreception and taste

olfaction

photoreception + visual sensory processing

signal → collection → transduction → processing → action

types of synapses

electrical by direct ion coupling

chemical with NT

electrical synapses: structure, vert/invert, current measured?, coupling coeff, advant/disad, squid + cockroach?, retina + heart?

* gap junctions: 6 monomers of connexin = connexons = pore which allows direct conductance of ions
* connexin = vertebrates, innexin = invertebrates
* current measured between pre/post synaptic cells (can be hard to distinguish for gap junx)
* **coupling coefficient**: gap junctions efficacy can be different = V2/V1 (decays over time)
* advantages of gap junx: rapid bc direct ion conductance
* disadvantages: little flexibility bc can’t control flow of ions in synaptic transmission
* giant squid axon + cockroach: use electrical synapses for fast escapes
* vert. retina + heart = synchronized

chemical synapses + postsynaptic receptors

* presynaptic: vesicles and NT release
* postsynaptic receptors: 1) ionotropic receptors 2) metabotropic receptors
* slower, flexibility higher, lots of vesicles, synaptic cleft, vesicles contain NT = chem signals = ligands, ligands bind postsynaptic R’s = neurotransmitter receptors
* ionotropic receptors: ligand-gated, direct, fast,
* metabotropic receptors: GPCR, slow, amplification, indirect, secondary messengers

fast chemical synapses example

postsynaptic density

synaptic potentials

synaptic currents

functional basis

* fast chemical synapses: neuromusclar junction → acetylcholine
* end plate region: unique structure, NMJ
* Schwann cell sheath: myelin PNS
* post synaptic density: dense aggregates (receptors) at the membrane
* functional basis: nerve is stimulated, recording potential in presynaptic cell, muscle AP, epp is unique to neuromuscular junctions which is higher than the threshold level of muscle AP

synaptic potential: graded change in resting membrane potential in post-syn cell

* epps: end plate potentials, not used in brain, neuromuscular junctions only
* PSP: post synaptic potential
* EPSP: excitatory postsynaptic potential (ex: epp)
* IPSP: inhibitory, drive the membrane potential away from threshold

synaptic currents: ion flow through channels in response to NT release, produces depolarization in rising phase of EPSP

* EPSC/IPSC: excitatory/inhibitory postsynaptic currents, trigger PSP’s

sequence of events of synaptic transmission at NMJ

1. AP arrives: generated at axon hillock, propagated to presynaptic terminal, role is to depolarize terminal in order to open Ca channels
2. VG Ca channel’s open: influx Ca so NT is released
3. NT (Ach) released: cannot be available all the time, Ach is quickly taken back up to stop contraction
4. ACh receptors open: Ach binds to ionotropic receptors Na / K channels, Na in, K out
5. EPSP: depolarization membrane
6. muscle AP - contraction
7. ACh degradation of AChE: Ach is cut by enzyme to make choline
8. recycled choline: choline taken back up by presynaptic cell and reused by adding a acetyl group back on

neuronal synaptic potentials resemble those @NMJ

2 factors that affect hyperpolarization

1. excitatory CNS synapse: glutamate in mammalial CNS
2. inhibitory CNS synapse: GABA

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* excitatory NT R: Na+ K+ ions
* inhibitory NT R: Cl- ions = hyperpolarize
* excitatory CNS synapse SMALLER than in muscle

2 factors: loosing positive charges + gaining negative charges (Cl-)

pros of chemical synapses v electrical - 4

* amplify current flow
* can be excitatory or inhibitory unlike electrical which are almost always excitable
* one-way: either excites OR inhibits, electrical can do both
* more modifiable in their properties: plasticity of NS, electrical are not flexible

2 major differences between neuronal + neuromusclar EPSP

* CNS vertebrates use glutamate instead of acetylcholine
* NMJ has larger EPSP than neuronal
* ACh gives greater EPSP than glutamate, GABA gives small IPSP

presynaptic release of neurotransmitters 4

1. neurotransmitters: Ach synthesized + stored in presynaptic terminal
2. voltage-gated and Ca2+ dependent
3. quantal + vesicular
4. synaptic vesicle recycling

neurotransmitters: 3 statues, 7 major types,

ways to terminate NT signaling 4

1. exogenous application of the NT → same physiological effects
2. must be released when presynaptic neuron is active
3. must be blocked by the same agents that block the transmission?

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* 7 major types: Ach, GABA, Glutamate, Dopamine, Serotonin, Nor-epi, glycine
* ionotropic: GABA, Ach, glutamate
* metabotropic: nor-epi, serotonin, dopamine
* termination of NT signaling:


1. enzymatic degradation:
2. reuptake: choline taken up by presynaptic + acetyl = Ach
3. enzymatic modification: NE is methylated = NE stops working
4. NT receptor desensitization: signal is terminated until receptor is able to recover - takes time

voltage-gated and Ca2+ dependence

* synaptic response is depolarization dependent
* **Block Ca2+ channels? block AP?**
* PSP is graded: stronger stimulation = more NT released, intensity dependent
* AP is all or nothing: as long as current is greater than threshold level it will occur
* depolarization = increases calcium influx = NT dependent release
* NT release is depolarization and Ca2+ release dependent
* Na Channel blocker = TTX
* K channel blocker = TEA

quantal release of NT

* miniature EPSP: smaller version of as neuromuscular EPSP, small depolarizations with no stimulation in response to A quantum, proves spont. release quantum
* quanta = multi-molecular packet = vesicles
* quanta was named before vesicles were discovered
* a physiological concept to vesicles
* more stimulation = more quanta released
* evoked miniature EPSP’s are quantal

vesicular release NT

vesicular explained via cellular/molecular


1. docking: place vesicle in correct place to release NT
* V-snare: protein on vesicle, synaptobrevin
* T-snare: syntaxin + SNAP 25
* vesicles move around randomly until V+T snare find each other
2. Ca2+ entry:
* AP depolarizes presynaptic terminal to open Ca channels
* **calcium sensor ?**
* synaptoagmin binds Ca2+, bound vesicle can fuse with membrane
3. fusion: releases NT
* NT release can be controlled by Ca

botox

cleaves synaptobrevin to stop overexcitation of cells, no docking, enzyme is stable

synaptic vesicle recycling 2

1. classical: requires ATP, clathrin-mediated: coated with clathrin, NT are fully released, slower, greater amplitude of PSP


1. kiss-and-run: don’t fully bind/fuse, fast, NT not fully released, no energy required, amplitude PSP is smaller

postsynaptic mechanisms: structure, function of NT receptors AChR’s

pentamer: 5 subunits: 2 alpha, beta, gamma, epsilon

subunits have 4 transmembrane domains M1-M4

M2 creates the channel

2Ach bind 2 alpha subunits

AChR gating by the alpha subunits → will only bind ACh

reverse potential: defintion, direction of __, sign of__

when Vm = Erev, how does current go with Ik and Ina dominant??

emf equation

max PSP

* reversal potential: the value of Vm that would reverse EPSP/IPSP
* look at the direction of ionic current and the sign of the postsynaptic potential reverse
* Ik is dominant towards Vm = ENa and hyperpolarization, current out
* Ina is dominant towards Vm=Ek and Ach release, current in
* emfx = Vm - Ex
* max PSP: emf = Vm-E, -90-(60) = -150mV

Ach receptor 3 names

* channel (2Ach bind)
* ligand gated
* non-selective cations

integration at synapses

* each neuron has more than one synaptic contant
* 1 neuron forms \~1000 synapses (1 soma?)
* bigger soma = less resistance
* more Na channels = fires more easily
* closer to axon hillock (further from soma) there are more Na channels where the synaptic potential can be greater than the threshold potential to generate an AP

spatial vs temporal summation

stimuli integration

spatial: multiple stimuli, synapses A+B+C+D generate AP

temporal: same synapse but sends signal at different times to generate AP (meets threshold)

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stimuli can be integrated: excitatory current + inhibitory current = difference, (bigger excite + small inhibitory = small excite)

synaptic plasticity

LTP: induction, maintenance, retrograde?

LTD

tetanus stimulation

changes in synaptic strength (spatial and temporal is similar but more basic and less important)

long-term potentiation: long-lasting enhancement of synaptic transmission following intense stimulation

induction: NMDA receptor-dependent

maintenance: Ca2+ dependent second messenger pathways → increase GluR sensitivity

retrograde signal → NO release to presynaptic terminals to increases NT release

long term depression: suppressing synaptic strength

tetanus stimulation: constant high freq stimulation?

glutamate, Ach

glutamate CNS primary excitation NT

Ach primary excitatory in NMJ

* glutamate receptors
* ionotropic
* non-cation channels

NMDA receptors vs nonNMDA-R

Ca role

* activated by glutamate


* NMDA able to conduct Ca ions and Na and K ions
* non-NMDA: small PSP
* NMDA: larger PSP, not easy to open, requires LTP to open, conducts Na,K,Ca,
* presynaptic signal opens glutamate Na/K channels = stronger stimulation, NMDA can open
* glutamate is caged and needs to be open
* Ca concentration increases → steps → generates retrograde signal generator (NO) → presynaptic terminal to enhance NT release
* Ca2+ can bind PKC calmodulin and kinases

doogie mouse

overexpression of NMDA receptors, causes increased intelligence/cognition

muscarinic vs nicotinic AChR

muscarinic: inhibitory, metabotropic, opens K channels = hyperpolarization, lowers heart rate

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nicotinic: excitatory, ionotropic in NMJ

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Ach typically excitatory but depends on the type of receptors

NT receptors for slow metabotropic actions - G-protein mediates synaptic transmission

metabotropic: no channel pore

G-protein alpha subunit activates ion channel, it can activate or inhibit

G proteins in postsynaptic cells act via intracellular effectors - 3

g proteins can act via non-cAMP signaling pathway - 3

1. NT can mediate different synaptic effects by activating different kinds of receptors
2. G protein: membrane-delimited action
3. ion channels can be gated by signal other than voltage or ligands

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1. IP3 and DAG
2. cGMP
3. direct modulation

3 things make synapse flexible

* flexibility of receptors and NT, ionotropic and metabotropic
* summation: temporal and spatial, signaling can be different
* synaptic plasticity

why muscles organized

in order to generate enough power

types of muscles

intercalated disk

striated: skeletal, cardiac

smooth

gap junction that has electrical synapse, used in heart muscles

skeletal muscle organization

what is the building block of muscle fibers

muscle fiber (cell)→ myofibrils → sarcomere → myofilaments → actin + myosin

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building block = sarcomeres

z disc to z disc

actin? myosin?

I band

H zone

M line

A band

z disc to z disc = 1 sarcomere

actin binds z disc, structural support, can see striation, thin filament

myosin = thick filament

I band = z discs are, actin only

H zone = only myosin, no actin

M line = bisects the H zone, myosin, center of sarcomere

A band = length of myosin

myofilament structure

actin: stabilize heavy chain structure, aka G-actin (globular), polymerization of G-actin forms chains of 2 stranded helix of F-actin, has myosin binding sites

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tropomyosin and troponin complex: enzymes that control/ regulate muscle contraction

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myosin: thick heavy chains = tails and head, light chain = hinge, molecular motor, myosin ATPase hydrolyzes ATP forms cross-bridges, has actin and ATP binding sites

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titan and nebulin provide structural support

muscle contraction

myosin ATPase = molecular motor

sarcomere length shortens

rigor mortis = ATP never binds to site = stiff body after death


1. actin bound to site on myosin = ATP site is free to bind, = rigor
2. ATP binds to ATP-binding site, conformational change, myosin and actin detach
3. hydrolysis of ATP by myosin, energy stored in cross-bridge, muscles are at REST
4. actomyosin: actin and myosin bind together, requires Ca2+, by energy provided by ATP hydrolysis ?
5. power stroke: myosin head cocks + actin slides = shortens
6. ADP unbound, new ATP binds to myosin head and releases actin

excitation-contraction coupling

muscle contraction is coupled with excitation

ATP + Ca2 = tension

No Ca2+ ATP = tension decreasing

ATP is not responsible for tension (muscle contraction)

Ca initiation muscle contraction

Ca2+ in excess increases muscle tension

Calcium concentration dependent contraction

role of calcium = cross-bridge attachment enhanced

ATP increases, myosin hydrolyses ATP more = more cross bridge cycles (1 ATP = 1 cycle, 2 ATP = 2 cycle… more cycles – more muscle contractions)

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3 components of troponin: prevent contraction

Troponin C: binds to Ca2+, conformational change, unblocks myosin binding site on actin, synaptotagmin?, binds myosin?,

Troponin I = binds to actin

Troponin T = binds to tropomyosin (which covers myosin binding sites on actin), pulls tropomyosin away exposing the site so myosin can bind and create crossbridges

When Ca2+ binds to troponin C, there is a conformational change, makes troponin I further away  

Troponin T is away from the actin binding site, myosin can bind

the triad

transverse-tubule + 2 sacroplasmic reticulums

T-tubule: Ach → EPSP, generates muscle AP which travels through t-tubule, DHP-R

SR: Ca2+ stores, RyR

DHP-R: voltage sensitive Ca2+ channel, when AP travels down t-tubule, opens channel, blocks RyR

RyR: becomes unblocked when DHP-R is open, releases Ca2+ which travel through DHP-R, sensitive to ryanodine

T-tubule and SR are connected, AP opens Ca channels, DHP-R blocks RyR, when DHP-R active it shrinks and calcium can be released from RyR and binds TN-C, then myosin binding side of actin exposed → powerstroke

summary of excitation-contraction coupling

1. AP in motor neuron → ACh release
2. Ligand-gated ACh channels open
3. AP in muscle → depolarizing T-tubules
4. conformational DHPR → RyR opens
5. Ca2+ release → TN-C
6. Cross bridges → power stroke
7. muscle contraction
8. Ca taken back up into SR when not needed

mechanics of muscle contraction

antagonistic pairs, isometric vs isotonic contractions, concentric vs eccentric

3 “types” of muscle contractions

elastic component

antagonistic pairs: skeletal muscles working in pairs, one muscle shortens and the other lengthens

isotonic contraction: IT: muscle generates enough tension to overcome load, goes above the force required for the load, type examples

* Concentric contraction: concentration moving closer to the center of the body, shortening conctration
* Contractile component: group of sarcomeres, actively contracting
* Eccentric contraction: muscle lengthening, happens like when walking downhill?, generates power, like when holding dumbbell and tending arm out = lengthening, muscle lengthening can damage muscles if lengthens too far, small lengthening room,
* Elastic component: tendon – serial, parallel - connective tissues / cell membranes surrounding muscles, passively stretching

isometric contraction: IM: muscle length does not change, muscles are contracted but length does not change, like when you try to move a wall (it doesn’t), tension is generated – force is required to move load - Muscle doesn’t overcome the load = length stays the same

3 types muscle contractions: isometric, isotonic, eccentric

length-tension relation

Active tension like upside down U, passive tension increases as active tension decreases

Passive tension: pulling a rubber band, there is a point where tension begins

Length-tension relation: not solely determined by contractile component, we need elastic component

Sarcomere length: 3 phases increases, plateau, decreasing

maximum muscle contraction = no power, shortest

maximum muscle length: stretched too far, not enough actin myosin overlap

length-tension math

Resting Tension

* Change Length
* Find Tension

Pre-load weight

* Change Tension
* Find Length

Contracting

* Passive → Active
* Change is either T or L

Work = force x distance

* gram x mm

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Resting tension: passive

Contracting: active

Work = F x d = tension x length = g\*mm = tension \* (length1 – length 2)

To find maximally shortened length: active curve, find where on the curve where x = y, then find parallel x? green + pink, have to look back to SHORTEST length, THEN substract the two numbers

fiber types in vertebrate skeletal muscle

swimmer vs cyclist

2 groups of muscles : tonic and twitch

Tonic fibers: no AP, yes membrane potential differences, don’t want eye to twitch,

Twitch/ phasic fibers: most musculoskeletal fibers, generate AP


1. Slow oxidative: SO, type 1: ATP steadily provided, contracts slowly, not easily tired – used for long term, O2 dependent require hemoglobin is why the slow oxidative is red, red colored cells, steak – red meat
2. Fast oxidative glycolytic, FOG type 2a: ATP provided by glycolysis, rapid repetitive movements, orange, in between rapid and long term, low fatigue
3. Fast glycolytic, FG type 2x: no oxygen needed, yellow/white, rapid contraction, chicken breast, fast fatigue

Black dots: capillary, surround red cells, do not surround yellow cells because they do not need oxygen,

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Second pictures:

Darker color = red , white color = FG is bigger, why? In order to supply oxygen need to be smaller = greater SA, but FG doesn’t need O2

Swimmer v cyclist: swimmer – short term sprints - have less red cells, cyclists – endurance training – have more red cells

types of skeletal muscle fibers:

name, myoglobin, metabolism, strength, fatigue resistance, capillary blood supply

energetics of muscle contraction: ATP use and regen

ATP consumption:

* myosin ATPase: detachment from actin, power stroke
* calcium pumps: pumps Ca2+ back into SR

ATP regeneration during muscle activity:

* high energy phosphatates (creatine-p)
* anaerobic glycolysis
* aerobic catabolism - used in type 1 fibers

speed of muscle contraction/relaxation

1. myosin heavy chain isoforms: the rate of ATP hydrolysis varies (SO = slow)
2. sequestration of Ca2+ by Ca2+ ATPAse: Ca2+ needs to be pumped back into SR

speed of contraction: FG > FOG > SO

different muscle types

color, diameter of fiber, levels of glycolysic enzyme, function in animal - SO FOG FG

SO: red, small diameter, low level of glycolytic enzymes, used in animal posture

FOG: red/orange, intermediate diameter, intermediate glycolytic enzyme, standing/ walking/ repetitive movements

FG: white, large diameter, high levels of glycoltic enzymes, jumping/ burst of fast running

muscle endurance vs resistance training

exercise: muscle in use

**endurance training**


1. endurance: FG → FOG fibers
2. angiogenesis: capillary density increases by VEGF (more VEGF expressed = more capillaries made) (VEGF increases w exercise)
3. density of mitochondria increases why? increased O2 levels, more ox phos needs to happen = more mito required

**resistance training**


1. hypertrophy: actin and myosin synthesis, myofibrils increase
2. FG → FOG fibers

**PGC-1a in endurance and resistance exercise**

* transcription coactivator binds to TF to regulates genes involved with energy metabolism, controls endurance and resistance training why? increase gene expression to increase synthesis of new components in training
* 2 different subtypes: PGC-1a1 and PGC-1a4
* PGC-1a1: endurance, increases VEGF, fatty acid oxidation, mitochondria, and myosin heavy chain 1 + 2
* PGC-1a4: resistance, increases IGF-1 and decreases myostatin

why? myostatin inhibits muscle mass increase, IGF-1 increases glycolysis, more ATP taken up, more glucose required to generate power

atrophy: muscle not in use

by denervation, tenotomy (cutting the tendon), immobilization, microgravity

few SO type 1 fibers

muscle atrophy with age = sarcopenia

EXCEPTION: black bears and aestivating frog hibernation… NO atropy why? how? they minimally maintain, oxidative stress reduction, SOD superoxide dismutase inhibits ROS

regulating muscle mass

homeostasis between hypertrophy and atrophy

PGC-1a, hypertrophy?

myostatin and PI3K-Akt1 pathway control hypertrophy and atrophy

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myostatin: negative growth regulator, myostatin mutants = double muscled, causes atrophy = muscle degradation, suppresses protein synthesis, increases atrophy genes

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PI3K-Akt1: hypertrophy, overall gene expression is increased, enhances muscle growth, Akt1-p inhibts myostatin binding

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neuronal control of muscle contraction

vertebrates:


1. antagonistic pairs - flexor and extensor muscles

bicep and tricep not working at the same time even tho they both are activated by Ach, one is contracting the other is not, pairs are not stimulated at the same time, only exception = shivering
2. excitatory Ach
3. increases muscle tension, muscle fiber tension is set, 1 AP causes 1 tension/twitch, how does muscle tension increase? Motor units
* no gradation in a motor unit but high-frequency AP
* activating more motor units
* different types of muscle fibers

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1 Motor unit = 1 motor neuron + all muscle fibers its attached to (\~2-3), we have several different motor units, motor units not overlapped, something is heavy? more motor units are used

Activating more motor units: continually stimulation from AP = tetanic stimulation, tension is at maximum

smooth muscle

no sarcomere, no t-tubule

more randomized, instead of z-disc = dense body

dense body: actin and myosin overlap and bind,

single unit SM: work through gap junction via electrical synapse, depolarize and contract together as one unit, myogenic = beginning in muscles (impulse comes from muscle), intestinal tract - moves as one

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multi unit SM: no gap junction, neurogenic = beginning in neurons (impulse originates from neurons), much easier to regulate power of muscle contraction, iris muscle - carefully controlled

contraction of smooth muscles

Ca from internal and external sources

* hormones and NT released
* G-protein linked Ca channel - metabotropic
* VG Ca2+ channel - ionotropic
* Ca from SR - not well developed in smooth muscles
* Ca binds calmodulin, binds and activates myosin light chain kinase, kinase phosphorylates myosin LC, activates myosin ATPase = begins contraction, phosphatase removes PO4 from MLC

Ca2+ pumps into plasma and SR

no troponin

myosin-linked regulation

contracts and variable, diverse, not designed to generate large power like skeletal muscles

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unusual features of SM contraction

latch state: vertebrates, ATP binding is very slow, cross-bridges are “latched” to actin and maintain tension without using ATP, termination: myosin LC dephosphorylation?

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catch state: invertebrates, mollusks, muscles are stiff and resistant to stretch, produced by the formation of a rigid network of connections between myofilaments, ACh can activate, serotonin relaxes, after the catch state Ca2+ should be gone from cytoplasm?

characteristics of 3 major types of muscles in vertebrates

cellular physiology

cellular signaling

membrane transport

neuronal communication

sensory system

motor structure and function

energetics of living cells

thermoregulation

systems physiology

lung + O2 → blood circulation → tissues

nutrients → blood circulation → kidney

thermoregulation: animal maintains its own body temp regardless of external temperature

circulatory systems

function: carry blood/hemolymph into close contact with every cell in the body

well developed structure: heart, arteries, veins, capillaries

two CV systems: open and closed

two types of CV circulation

1. open CV:
* blood circulated slowly
* contained in space called hemocoel
* baths tissues freely in blood (not circulated through capillaries)
* 20-40% of body volume is hemolymph
* blood pumped through heart
* low pressure
* disadvantages: slow nutrient delivery, gas exchange, and metabolic rates
* advantages: no BP, less energy required, better regulation of body temperature
2. closed CV:
* blood is compartmentalized from other body fluids
* smaller volume
* rapid distribution
* divided heart allows different pressures in pulmonary and systemic loops
* disadvantages: requires lots of energy
* advantages: less volume \~5% body, rapid distribution

overview of mammalian circulatory system

propulsive organ = heart

blood vessels = arterial and venous systems, capillaries

distribution of blood throughout vascular tree

arteries \~16-18%

capillaries \~ 5-7%

veins \~ 50%

heart \~15%

pulmonary system \~12%

physical and mechanical properties of cardiovascular system 4

flow: movement of blood is controlled primarily by the heart

pressure: hydrostatic/hydraulic pressure

resistance: law of bulk flow and ohms law

velocity: depends on part of circulatory system

flow rate

how much blood flowing at a given time

F = /\\P/R = law of bulk flow

most important

peripheral blood flow = not heart

central circulation = heart

cardiac output (Q) units volume pumped per unit time

Q = V x F

V = stroke volume = volume ejected in one contraction

F = frequency of heartbeats beats/min

stroke volume

SV: the difference between EDV and ESV, blood left over in heart?

SV = EDV - ESV

EDV: end-diastolic volume, before contraction, heart is fully relaxed, highest amount of blood,

ESV: end-systolic volume, end of contraction, smallest volume, maximum blood ejected

high BP = hard to eject blood

SV varies with HR, pressures in atria ventricles, aorta etc

average volume and flow and cardiac output in humans

V = 70 mls F = 72 beats/min

cardiac output through aorta = 5040mls / min

flow remains equal when viewed collectively in all compartments

closed system = smaller volume = more efficient

pressure

mmHg torr Pa

blood pressure: hydrostatic + hydraulic

hydrostatic pressure: force exerted against wall, static

hydraulic pressure: pressure in fluid which is in motion, moving water

goes down pressure gradient high → low

flow is proportional to the ___

difference in pressure /\\P

pressure gradient is important

at high and low pressures, same resistance, flow can be the same

ex: P1: 100mmHg P2: 80mmHg AND P1: 50mmHg P2: 30mmHg, /\\P = 20mmHg for both

resistance

relationship between pressure and flow

the law of bulk flow or ohms law

flow between two points is proportional to the pressure difference AND inversely related to the resistance

Flow = /\\P/R

higher resistance = flow rate decreases

flow is inversely related to resistance

Q = /\\P/R I = /\\E/R

as resistance increases, flow decreases

things that increase R: 1) small tube radium 2) long tube length 3) high fluid viscocity

which is most important? radius

vasoconstriction and vasodilation: changing tube radius, practical way to regulate cardiovascular system

pressure decreases with increasing ______

place of highest pressure change

major site of resistance

largest blood vessel

smallest diameter

distance from the heart

arterioles are major site of resistance, mainly due to sharp decrease in radius

arterioles have greatest drop in pressure, they have the largest drop in size between aorta and capillaries

vena cava = largest blood vessel

capillaries diameter is the smallest \~6-10um

resistors in series vs parallel

series: Rtot = R1+R2+R3

parallel: 1/Rtot= 1/R1 + 1/R2 + 1/R3

if R’s are the same

series: 3R parallel: 1/3R

parallel resistors make it easier to reduce resistance and increase flow which makes CV work less

series resistors make flow slower

most vascular beds are arranged in parallel → minimizes resistance

entire circulatory system cardiac output

Q = mean blood pressure / total peripheral resistance

peripheral circulation

arterial system

venous system

capillary exchange

anatomy of arteries, veins, capill, very different because of different pressures

atrial system: deals with highest pressure, more thick = less compliant, smooth muscle

venous system: thin and compliant, like a balloon?, vena cava lowest blood pressure,

arteries

4 functions

get stiffer, less compliant, smaller with increasing distance from heart → PRESSURE RESERVOIR

4 functions:

1) passage of blood to capillary system + venial system

2) pressure reservoir: diastolic = lowest pressure, systolic = pressure high, the average pressure maintain by heart is lower than arterial why? heart is contracting much bigger, arterioes are not relaxing as much as the heart = higher pressyre

3) dampening of pressure, when pressure gets to capillaries there is no more oscillations

4) control of blood distribution: precapillary sphincters, more blood to stomach during digestion

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at periphery, pulse pressure oscillations are much reduced and resistance in arteriolar beds controlled by vasoconstriction

diastolic = relaxing, systolic = contracting

peripheral circulation 3 parts

1) arterial system 2) venous system 3) capillary exchange

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arterial system: highest pressure = pressure reservoir, more thick = less compliant, thick smooth muscle?

venous system: highest volume, thin + compliant, vena cava = lowest blood pressure

anatomy of arteries, veins, capillaries are very different because of different pressures

arteries

4 functions:


1. __passage of blood__ to capillary system + venous system
2. **pressure reservoir**:
3. __dampening of pressure:__ when pressure reaches capillaries it is no longer oscillating,
4. __control of blood distribution:__ precapillary sphincters

gets stiffer, less compliant, smaller with increasing distance from heart

at periphery, pulse pressure oscillations are much reduced and resistance in arteriolar beds controlled by vasoconstriction

diastolic: relaxing

systolic: contracting

why is average heart pressure lower than arterial pressure

heart contractions are much bigger (big oscillations), arterioles are not relaxing as much as heart (smaller oscillations at higher pressure)

compliance in venous system

compliance: volume change when there is a pressure change, bigger volume change = more compliant

change in volume (V) / change in pressure (Ptm: transmural)

* high compliance: small increases in pressure produce larger increases in volume
* lower compliance: stiff, takes more pressure to increase volume

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11 mmHg \~10% of arterial pressures

\~25-30 fold more compliant than arteries

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less elastic tissues = less recoil = greater compliance

act as volume reservoir, susceptible to venous pooling

blood vessel lining is very thin = easy to increase volume

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veins can vasoconstrict

sympathetics adrenergic fibers can change their compliance → occurs after hemorrhage to compensate for reduced venous volume, also shifts with position (laying down to standing up)

capillary exchange: types, structure, functions, regulation of functions

3 types capillaries:


1. continuous
2. fenestrated
3. sinusoidal

structure:

* one cell layer of endothelial cells, no smooth muscles, 6-10 micrometer diameter
* precapillary sphincters: can allow or block blood flow
* autonomic input: controls precap-sph, can redirect blood flow to areas that need it
* microcirulatory bed: venule, arteriole, precap-sph, capillary, RBC, etc

filtration and diffusion:

starling forces: blood pressure and osmotic pressure

types of capillaries

found in body where

Continuous: small cleft 4nm wide, AA and glucose cannot pass, ions can pass through and water, exchange is minimal, largely found in brain, muscles, lung

Fenestrated capillary: like window, glucose and small AA can pass, in between continuous + sinusoidal, kidney allow glucose to pass through,

Sinusoidal: really big to pass proteins, found in liver, paracellular gap

movement of substances across capillary walls - 3 mechs

diffusion: random molecular motion

* Ficks Law: Flux, Js = D*** A \* (C1-C2) / thickness

filtration/reabsorption: net movement due to fluid (blood) or osmotic pressure

* more related to circulatory system
* osmotic pressure + blood pressure contribute to direction of material movement

transcytosis:

* endocytosis, vesicular transport, exocytosis
* large proteins across epithelium
* unique to capillary

starling forces in capillaries

blood pressure > osmotic pressure = filtration

blood pressure < osmotic pressure = uptake

filtration more towards arterial end of cap

uptake more towards venous end of cap

**blood pressure = driving force for filtration**

**osmotic pressure = driving force for uptake**

blood hydraulic pressure decreases along cap

colloid osmotic pressure = oncotic pressure

osmotic + blood pressure regulate filtration and uptake

flux across capillaries

reflection coefficient

J = \[K(Pcap-Pint)\] - \[o(pi-cap - pi-int)\]

Pcap leaves cell? pi-cap enters cell?

Pcap = capillary blood (hydraulic) pressure

Pint = interstitial fluid pressure

pi = osmotic pressure

K = Coefficient of Hydraulic Conductivity

sigma, o = Reflection Coefficient

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Sigma: highest - continuous (x\~1) > fenestration (0