Human Physiology Midterm #2

Lecture 11

11

spinal cord

composed of inner core of gray matter & outer core of white matter

surrounded by vertebral column

part of CNS

ends at L2 vertebra

• nerves extend from cervical → thoracic → lumbar → sacral → coccygeal, total of THIRTY-ONE pairs

cauda equina

area after L2 where spinal cord has ended

myelinated axons

where spinal tap happens

(sacral + coccygeal + lower lumbar nerves)

dorsal & ventral horn

made from gray matter on inside of spinal cord

looks like an H, dorsal horn is top half of H facing back

• dorsal→ sensory neurons

• ventral→ motor neurons

ascending & descending bundles

ascending are myelinated axons that carry info to brain

desceding are myelinated axons that carry commands to motor neurons

afferent fibers

start in periphery and end in dorsal horn

located in dorsal root ganglia → has cell bodies of afferent neurons

• dorsal roots→ afferent limb of each spinal nerve, found in vertebral canal

efferent neurons

carries motor information

cell bodies are in spinal cord

spinal nerves are <1cm

• formed by dorsal and ventral roots from same level combining

PNS organization

PNS → autonomic(involuntary) neurons & somatic(voluntary) neurons

autonomic→ sympathetic (excite) & parasympathetic (rest)

PNS function

transmits signals btw CNS and effectors throughout the body

• autonomic neruons→ control glands and muscles of internal organs

• somatic motor neurons→ control skeletal muscles

somatic motor neurons (innervates skeletal muscle)

cell bodies are in brainstem or ventral horn

leaves CNS and pass to skeletal muscles WITHOUT any synapses

release ACh (acetylcholine)

only contracts when excited, no inhibition of skeletal muscles

autonomic neurons (innervates heart, smooth muscle, glands, GI)

made of 2 neurons connecting CNS and effector cells → 1 inside CNS & other is autonomic ganglion

pre & postganglionic neurons release ACh (NT released btw postganglionic neuron and target is diff btw sympathetic & parasympathetic division)

can be inhibitory or excitatory

divided into sympathetic & parasympathetic

dual innervation

parasympathetic & sympathetic parts of autonomic NS innervate almost every organ

• sympathetic: fight or flight (↑HR, ↑blood flow, ↑lungs)

• parasympathetic: rest & digest (↑digestion, ↑secretions, ↑liver/kidneys/bladder, ↑sex)

sympathetic & parasympathetic leaving CNS

sym: leaves from 2ndL & 1stT regions, ganglia are close to spinal cord and make sympathetic trunks/chain (has postganglionic cell bodies) (looks beaded)

para: leaves from brainstem & sacral areas, ganglia lie inside or v v close to organs that it innervates

• vagus nerve: originates in medulla oblongata and carries 75% of all Psym fibers

adrenal medulla

is a modified sympathetic ganglion

chromaffin cells release catecholamines (80% epinephrine, 20% norepinephrine) for fight or flight

epinephrine/norepinephrine

this NT is released btw sympathetic postganglionic neurons & effectors

receptors in PNS

ACh receptors present and are effected by agonists(trigger pathway) & antagonists(don’t trigger pathway)

• nicotinic ACh receptor → responds to nicotine

• muscarinc ACh receptors (M-AChR) → responds to muscarine (mushroom), in autonomic NS

  • atropine is an antagonists of M-AChR

Adrenergic receptors also present

• activated by epinephrine & norepinephrine

cells charge

intracellular:

• slightly negative

• K+ is major cation

• Po- is major anion

extracellular:

• slightly positive

• Na+ is major cation

• Cl- is major anion

law of conservation

net amount of electrical charge must be zero

• also note that separating + & - charges takes energy

• material charges move thru is a conductor (water), separated charges can’t move through insulator (CM)

cell membrane

enables separation of electrical charge in body, not permeable to ions

to create a membrane potential difference → use active transporter to move ions against conc gradient → creates an electrical gradient (diff in net charge btw inside and outside) & concentration gradient (more ± outside compared to inside) → electrochemical gradient

• electrical gradient btw extracellular fluid and intracellular fluid → resting membrane potential

relative electrical gradients

relative scale measures difference in charge using a voltmeter → used for living systems

absolute scale means counting # of ions on either side of plasma membrane

• voltmeter: uses 2 electrodes filled with conductor to measure electrical difference btw

  • RECORDING electrode goes from CM into cytoplasm & REFERENCE electrode is placed in external bath → recorder usually reports resting potential of -40 to -90mv

K+ leak channels

in CM, allows K+ to leak out of cell moving down conc gradient → creates a negative charge inside cell → electrical gradient

opp charges attract so K+ is being pulled back inside by negative ions → eventually driving force of K into cell = chemical conc gradient driving K out → net movement of K stops

resting membrane potential is mostly due to movement of K+ out of cell down its conc gradient (makes inside cell more neg) BUT small # of Na+ channels are open in resting state so some Na+ move into cell

equillibrium potential (Eion)

uses Nernst equation to calculate: Eion(x) (equilibrium potential for ion) , when cell is permeable to only 1 ion(x)

61 is Faraday’s constant

concentration gradient

the greater the membrane permeability to an ion the greater the contribution that ion species will make to the membrane potential

GHK equation

calculates relative membrane permeabilities for Na+, K+, Cl-

(Cl is reversed because its an anion)

usually around -70mV

Na/K ATPase pump

maintains Na & K concentrations

pumps 3 Na+ out for every 2 K+ pumped in → makes cell inside more negative and creates small electrical gradient which maintains conc gradient

2 types of changes in membrane potential

graded & action potentials

graded potential

transient changes in membrane potential that occur in dendrites or cell body, confined to small area of CM

charge flows from place of origin to adjacent regions, after depolarization by chemical signal → opens cation channels → makes a less negative potential in that area → + charges in cell flow away from depolarized region and move towards more negative membrane areas → outside cell + charges flow from positive membrane towards less positive regions

charge is lost across membrane thru membrane permeability/leakage

summation

when additional stimuli occurs before graded potential has died away

will be added to depolarization from first

action potentials

changes in membrane potential starting in trigger zone and propagated down axon

polarized

outside and inside of cell have a diff net charge

depolarized

membrane potential becomes less negative (towards 0)

overshoot

reversal of membrane potential resulting in inside of cell becoming positive relative to outside

repolarizing

depolarized membrane returning towards resting value

hyperpolarized

potential is more negative than resting level

if an ion concentration increases outside the cell, the equilibrium potential

will increase to oppose movement of ion

equilibrium potential and electrical gradient should always be equal and opposite to achieve electrochemical equilibrium

electrical potential vs chemical gradient

electrical potential→ ion moving according to charge, opp charges attract and move tg

chemical gradient→ ion moving from high to low conc regardless of charges

all mammalian cell types have a separation

of positive and negative charges across CM

action vs graded potentials

all cells can conduct graded potentials but only excitable CMs (neurons, muscle cells, endocrine/immune/reproductive) can have action potentials

• this happens through voltage gated ion channels → open or close in response to changes in membrane potential (mostly Na+ or K+)

Na+ & K+ channels

both reversibly change shape

Na+ → responds QUICKLY & opens well before K+ channels, closes faster during repolarization as well

• have inactivation gate that limits Na+ flux by blocking channel, closed → open → inactivated → closed ….

K+ → responds slower

action potential steps with ligand gated channels

1. stimulation of LG channels depolarizes membrane to threshold membrane potential

2. when threshold value is reached (-55mV) → Na+ channels open and increases depolarization (+ feedback)

3. + feedback loop creates overshoot of membrane potential

4. as membrane potential peaks Na+ permeability declines as inactivation gates break + feedback loop by blocking Na+ channels

5. depolarized membrane causes K+ channels to open → K+ flows out of cell → repolarizes membrane towards resting value

6. repolarization causes Na+ channels to go from inactivated to closed & for K+ channels to close

   1. before closing K+ channels the membrane gets slightly hyperpolarized before evening out to resting (-70mV)

subthreshold potentials

depolarizations less than threshold value

action potentials will not occur → will return to resting potential after stimulus is removed

action potentials are all or none

EPSP (Excitatory PostSynaptic Potential)

a depolarizing graded potential that makes a neuron more likely to fire an AP

IPSP (Inhibitory PostSynaptic Potential)

a hyperpolarizing graded potential that makes a neuron less likely to fire an action potential

absolute refractory period

when VG Na+ channels are inactivated → inactivation can only be removed by membrane repolarization

so a second stimulus will not make a second AP during this time

• after absolute refractory period is the relative refractory period

relative refractory period

some (not all) of VG Na+ channels are in closed state & some K+ channels are open → new stimulus can depolarize membrane above threshold BUT only if it is big or lasts longer than the absolute refractory period

inside vs outside the cell conc

sodium is > outside

potassium is > inside

chlorine is > outside

trigger zone

where action potentials start and travels down axon terminal

action potentials can travel over long distances without losing amplitude

triggered by depolarizing graded potentials in dendrites that reach threshold value

Na+ & K+ channels open or closed during AP phases

resting→ Na is closed, K is closed

depolarization→ Na open, K closed

repolarization→ Na inactivated, K open

hyperpolarization→ Na closed, K open

hyper/hypo kalemia

hyperkalemia→ high blood potassium

• most dangerous as it makes it harder to start an action potential in heart because it is hyperpolarized

hypokalemia→ low blood potassium

• dangerous as it gives depolarization of heart cells since less K leaves cell

axon potentials don’t occur on dendrites

because they require VG Na+ channels (which open at threshold potential) and these channels are only in axon hillock (not in dendrites or cell body)

propagation of AP

membrane depolarization @ trigger zone opens Na+ channels → further depolarizaiton → + charges flow from depolarized trigger zone spreads to adjacent sections → flow of current towards axon terminal creates conduction of AP (feedback loop)

positive feedback loop of AP

when point B depolarizes it opens Na+ channels → @ point A the Na+ channels are inactivated while K+ channels are open → K+ leaves and repolarizes membrane → positve charge from B flows backward (to A) and forwards to C but backward has no effect because it is in absolute refractory period

AP CANNOT MOVE BACKWARDS

myelinated axons

APs travel faster across

myelinated axons limit touching with extracellular fluid → bare sections are nodes of ranvier

unmyelinated axons have current leakage because axon membrane is in contact w extracellular fluid where there are leak channels

nodes of ranvier

every node has lots of VG Na+ channels → Na+ ions entering at node increases depolarization and restores/regenerates amplitude of AP as it passes from node to node

• jumping of AP is called SALTATORY CONDUCTION

electrical synapses

occurs mainly in neurons of CNS (also in glial, cardiac, smooth muscle)

flows in BOTH directions

has rapid conduction of signals from cell to cell that synchronizes activity within a network of cells

chemical synapses

use NTs to pass information from presynaptic neuron to postsynaptic cell

NT cross synaptic cleft after being released from synaptic vesicles

ONE WAY conduction

structure: in postsyn membrane there is PSD (post synaptic density) which is protein dense area that ensures receptors are close to presynaptic NT release sites

NT release mechanism

AP reaches terminal of presynaptic membrane → terminals have VG Ca, K, & Na channels so when depolarization occurs it opens Ca channels and Ca flows into axon terminals → Ca activates fusion of vesicles w terminal membrane → Ca binds synaptotagmin & SNARE which anchor vesicles to CM and undergo conformational change to stimulate vesicle fusion w CM → after fusion vesicles either kiss and run or completely fuse

to remove NT from synaptic cleft

• diffusion

• enzymatically transformed into inactive substances

• actively transported back into presynaptic axon terminal (reuptake)

diff types of muscle

skeletal

cardiac

smooth

skeletal

attached to at least 2 bones by tendons

moves skeleton

multinucleate, unbranched, voluntary

cardiac

heart

pumps blood

1 or 2 nuclei, branched, non-voluntary

smooth

intestines/arteries

moves food

1 nucleus, unbranched, non-voluntary

muscle structure

entire muscle is coated with epimysium (also attached to tendon) → all fascicles are surrounded by 1 large epimysium and perimysium surrounds groups of fascicles → endomysium surrounds individual muscle fibers → sarcolemma → muscle fiber/cell

sarcoplasm

muscle fibers cytoplasm → helps muscle contract

full of myofibrils

• sarcolemma is CM of muscle fiber

myofibril

help contract/relax muscle

organelles in sarcolemma

composed of repetitive units → sarcomeres

sarcoplasmic reticulum

surrounds each of myofibrils and helps activate muscle contraction

sarcomere

has thick (MYOSIN (II) ) & thin (ACTIN) filaments

makes muscle striped/striated

contractile units of muscle

myosin

myosin I→ carries substrates as a single unit

myosin II→ forms dimer (2 tails twist around to form coil) → creates thick filament and heads stick out from strand and interact with actin (thin) filaments

• heads have actin-binding site & enzymatic domain that hydrolyzes ATP

sarcomere structure

has repeating I band→ A band → I band

sliding filament theory

muscles contract by shortening by all sarcomeres

no change in length of filaments → they slide past each other and increase overlap

myosin activity cycle

1. ATP binding to myosin head makes it detach from actin filament (this allows sliding, w/o ATP → rigor since all myosin is still attached to actin)

2. ATP hydrolysis makes head move into ‘cocked’ position → myosin binds weakly to new actin

3. binding of myosin to actin makes conformational change → releases Pi (inorganic phosphate from ATP hydrolysis)

4. release of Pi initiates power stroke → returns head to initial uncocked position → release of ADP

troponin

on actin

made of 3 subunits → one is a Ca2+ binding subunit called TnC (TnI, TnT)

tropomyosin

on actin

rod shaped protein that overlaps w 7 actin monomers that cover myosin binding sites

Ca2+ binding

to troponin makes conformational change that shifts tropomyosin into position → reveals myosin-binding sites on actin

allows binding

T-tubules & sarcoplasmic reticulum

work tg to contract muscle

AP follows T-tubules into deep muscle fiber → Ca gets released from sarcoplasmic reticulum → Ca & ATP are needed for myosin/actin interaction → after AP is over Ca is pumped back into sarcoplasmic reticulum by Ca2+ pump proteins

calcium is released by ion channels in sarcoplasmic reticulum CM

AP triggers conformational change in DHP in T-tubules → opens the ion channel ryanodine receptor → releases Ca into cytoplasm

anatomy of sarcomere

region of myofibril btw 2 Z discs

A is thick filament, B is thin filament

A band

extends length of thick filament and small part of thin filament

I band

area btw ends of thick filaments, only encompasses thin filament

H zone

areas btw ends of thin filament, only encompasses small part of thick filament, in middle of A band

Z disc

vertical line separating each sarcomere, in middle of I band

M line

vertical line that connects thick filaments, in middle of H zone

shortening is limited in muscle contraction

only so much overlapping can occur, Z discs may run into ends of thick filament

when contraction occurs→ thin filaments slide past thick, H & I bands get smaller, overlap increases, width of A band is constant

motor neurons

only activating a motor neuron can activate an AP in skeletal muscles

located in ventral horn of spinal cord/brainstem

myelinated and largest axons in entire body → propagate signals at high velocities

motor unit

a motor neuron + muscle fibers it innervates

when AP occurs in motor neuron → all muscle fibers in its unit contract

muscle fibers in 1 motor units are in one muscle but scattered throughout muscle

NMJ (neuromuscular junction)

junction of axon terminal w motor end plate (muscle fiber CM)

vesicles found within axon terminals of motor neuron have NT ACh

interneuronal synapses vs neuromuscular junction

ISPS don’t occur in humans ALL NEUROMUSCULAR JUNCTIONS ARE EXCITATORY

depolarization of 1 motor end plate (EPP) is >>>> excitatory graded potential (EPSP) because @ NMJ a NT is released over large area and binds/open more N-AChR → every AP in motor neuron makes an AP in each muscle fiber

tubocurarine

active ingredient in curare, neuromuscular blocking agent → muscle relaxant

nicotinic ACh receptor are in motor end plate → tubocurarine binds and competitive binds to stop ACh from binding → stops depolarization → flaccid muscle paralysis

blood / plasma

cells in plasma (water)

made of plasma, leukocytes, platelets, hematocrit

all blood constituents are moved thru body tg in 1 direction → bulk flow

• plasma makes up 55% of blood volume

• leukocytes + platelets make up less than 1%

• hematocrit (erythrocytes→red blood cells) makes up 42-45%

cardiovascular system

has 2 circuits and heart is divided into 2 halves each with an ↑atrium & ↓ventricle

blood flows from atrium to ventricle

deoxygenated blood is moved from right ventricle into pulmonary circuit to lungs → oxygenated blood is returned into left atrium → oxygenated blood is moved from left ventricle into systemic circulation of whole body

arteries & veins

Arteries carry blood AwAy from heart

veins carry blood to heart

blood flows from high pressure to low pressure

heart creates high pressure when it contracts

highest pressure is in aorta, lowest pressure is in venae cavae before it empties into right atrium

aorta → arteries → arterioles → capillaries → venules → veins → venae cavae

Flow calculations

∆P (pressure diff) = P1-P2, measured in mmHg → higher the pressure the greater the fluid flow

Flow = ∆P/R (flow is inverse to pressure)

Resistance (R) = (8 L (length of tube) n (viscosity of fluid)) / (pi * r^4 (radius of tube))

• length and viscosity won’t change in adult human, but BUT radius can

• vasoconstriction: ↓ blood vessel diameter

• vasodilation: ↑ blood vessel diameter

heart structure

outer pericardium layer & inner epicardium

wall of heart is made of myocardium (cardiac muscle cells)

inner surface of chambers in lined with endothelial cells

heart valves (AV)

called AV (AtrioVentricular) valves and have one-way flow

• left AV (MITRAL/BICUSPID)→ has 2 flaps

• right AV (TRICUSPID)→ has 3 flaps (Right Side has Tricuspid)

interventricular septum→ muscular wall that separates ventricles

during ventricular contraction the AV valves are closed to prevent blood flow back into atria

heart valves (SL)

semilunar and have one-way flow

from right ventricle into pulmonary artery→ pulmonary valve

& left ventricle into aorta → aortic valve

lets blood flow into arteries during ventricular contraction but stops blood from moving in opp direction during ventricular relaxation

heart/myocardial cells gets blood supply via

coronary arteries that branch from aorta

cardiac veins drain into coronary sinus vein which empties into right atrium

AP in heart starts

atria contract first then ventricles

gap junctions connect myocardial cells and allow AP to spread → depolarization from AP starts in SA (SinoAtrial) node in right atrium near superior vena cava → AP spreads then to atria then ventricles

steps for AP throughout the heart

1. atrial excitation→ depolarization of SA node generates AP that depolarizes all other cardiac muscle cells → SA node determines heart rate

2. atrial excitation ends→ depolarization spreads thru muscle cell of atria, left & right atria contract @ same time

3. ventricular excitation→ AP propagates AV node very slowly (allows for atrial contraction completion) → depolarization of AV transmits AP down to Bundle of His

   1. Bundle of His & AV node are only electrical connection btw atria & ventricles

4. ventricular excitation ends→ depolarization/contraction starts in apex of ventricles then spreads upwards → this makes a contraction that moves blood up towards semilunar valves

L-type Ca+ channels (long lasting)

cardiac cells uniquely have L-type Ca channels open→ influx of Ca keeps membrane depolarized at plateau level