Physiology Exam 1: Slides 1-185, Exam 2: slides 185-

Normal potassium

- more polarized ( -) resting membrane potential = higher driving force ( willingness to move) out of the cell

- more depolarized ( +) = lower driving force to leave the cell

Hyperkalemia

high levels of potassium in the blood

Hyperkalemia - why does this occur

kidneys not excreting potassium well

hyperkalemia effects

-RMP of cell and nerves

- blood becomes more positive ( more K+ extracell) -- more depolarization (+)

- fires Action Potential when they shouldn't ( due to the voltage being closer to 0)

Depolarization

a decrease in membrane potential (the interior of the neuron becomes less negative)

- the Na+ voltage gated channel opens

The membrane potential graph

Repolarization

Return of the cell to resting state (-70mv), caused by reentry of potassium into the cell while sodium exits the cell.

- K+ voltage gated channel opens

hyperolarization

the inside of the membrane becomes more negative than the resting potential ( -70mV to -75mV

Excitability

RMP closer to threshold = more excitable

RMP farther from threshold = less excitable

Graded Potentials ( a type of local potentials, synaptic, receptors)

- Hyper polarizing (-) or depolarizing (+)

- mediated via ligand-gated (chemical) channels

- height ( AP) magnitude dependent on stimulus strength

- decremental signal w/ distance

- can sum

-form on receptor endings

-short lived

Action Potentials, not local

- depolarizing (+)

- mediated via voltage- gated channels

-height ( AP) magnitude independent on stimulus strength

- cannot sum

Intracellular is..

2/3

Extracellular is...

-outside cells

made of :

1) interstitial fluid

2) Plasma

BOTH ABOVE HAVE SIMULAR IONIC COMPONENTS

Homeostasis

Physiological variables in a state of DYNAMIC CONSTANCY

- NOT A STATIC PROCESS

Homeostatic Control Systems

- the activities of cells , tissues , and organs regulate and are integrated to respond to any change in the internal environment. These systems work together to respond to the change and keep homeostasis

Steady State

When the variable for instance temp isn't changing but energy for instance heat must be added to maintain a homeostatic condition

resting membrane potential

The steady potential of an unstimulated cell

- all or none

Equilibrium

When the variable isn't changing but no input of energy is required to maintain homeostasis

Negative feedback

Increase or decrease in variable

- RESPONCE MOVES IN OPP DIRECTION

Negative Feedback - blood sugar

-glucose levels rise

-pancreas released

-in response to insulin, target cells take up glucose and the liver converts glucose to glycogen.

-blood glucose levels fall

-pancreas releases glucagon

-in response to glucagon the liver breaks down glycogen and releases glucose into the blood

-blood glucose levels rise

Positive Feedback

Feedback that tends to magnify a process or increase its output.

- EXPLOSIVE

- less common

- ex: pregnancy

KNOW THE ACTION POTENTIAL DIAGRAM ( LECTURE 1, SLIDE 22)

NA

Ionic basis of resting potentials

-cell if most permeable to K+

- inside the cell is negative relative to outside as more Na is inside and more K+ is outside

sodium-potassium pump

-a carrier protein that uses ATP to actively transport 3 sodium ions out of a cell and 2 potassium ions into the cell

-against their gradients

K+ leak channels ( A LOT)

ion channel permeable to K+ that us ALWAYS OPEN largely responsible for the resting membrane potential in animal cells

- K+ out, Na in

Na+ leak channels (A FEW)

- same for K channel, but NA IN, K out

- both go along their gradients

K+ voltage channels

- go along their gradient

- Na+ in, K+ out

The normal target value or level of a variable that the systems works to maintain is called the ...

SET POINT

membrane potential

the voltage difference across a membrane

Hyper vs hypokalemia

Hyperkalemia= increased K+ outside ( in blood)

- depolarization

Hypokalemia + decreased K+ outside (in blood)

- polarization

Hypermatremia

- higher extracellular NA+

-higher driving force outside cell ( polarization (-) )

- MAKES NA+ RUSHES INTO CELL via VG channels VS NORMAL LEAKING

-higher AP spike as this is dependent upon NA+ VG channels ( why hyperkalemia AP doesn't change)

Resting Membrane Potential ( dependance)

- dependance on changes in K+

- leak channels

Action Potential Spike Height ( dependance)

- dependent on changed in Na+

- VG Na+ channels open when reaching spike height

Action Potential Duration (dependance)

- dependent on changes on K+

-VG K+ channels in repolarization phase of AP

threshold potential

The minimum membrane potential that must be reached in order for an action potential to be generated.

-Na

Resting Potential is affected only...

an ion can only affect the resting membrane potential if the cell is permeable to that ion

escitatory synapse

- when a postsynaptic neuron is brought closer to the threshold (depolarized)

- Na flows into the cell

inhibitory synapse

- prevents a postsynaptic cell from approaching threshold by hyper polarizing or stabilizing the membrane potential

- K flows OUT w/ gradient

- more + are leaving the cell

convergence and divergence

photo

Electrical synapses

- gap junctions that allow current to flow between adjacent cells

- presynaptic - gap junction- post synaptic

- CELL TO CELL

chemical synapses

- neurotransmitters stored in synaptic vesicles are released by a presynaptic axon terminal into the synaptic cleft

- Signal then goes from the presynaptic neuron to an adjacent postsynaptic neuron at the postsynaptic density

Steps of neurotransmitter release

!) release i initiated when an action potential reached the presynaptic terminal membrane

2) voltage-gated Ca 2+ channel open

3) Calcium enters axon terminal

4) neurotransmitters are RELEASED into the synaptic cleft

5) Neurotransmitters binds to postsynaptic receptors ( LIGAND GATED CHANNELS

know this ;)

inotropic receptors

- receptor and a channel

- ligand binds, channel opens, ions follow

metabotropic receptors

- receptors that are associated with signal proteins and G proteins

- ligand creates some kind of 2nd messenger cascade

A drug might .....

•increase leakage of neurotransmitter from vesicle to cytoplasm, exposing it to enzyme breakdown.

( ACETYKCHOLINESTERASE AchE = ACITIC ACID+CHOLINE)

•increase transmitter release into cleft.

•block transmitter release.

•inhibit transmitter synthesis.

•block transmitter reuptake.

•block cleft or intracellular enzymes that metabolize transmitter.

•bind to receptor on postsynaptic membrane to block (antagonist) or mimic (agonist) transmitter action.

•inhibit or stimulate second-messenger activity within postsynaptic cell.

SSRIs

(selective serotonin reuptake inhibitors)

- block reuptake protein

- more serotonin stays in synaptic cleft

- more post-synaptic excitation

Benzodiazepines

-xanax, valium

- GABA agonists

- more info needed

local anesthetics

- procaine

(Novocaine) and lidocaine (Xylocaine) because these drugs block voltage-gated

channels → preventing them from opening in response to Na+ depolarization

- WITHOUT AP, signals don't reach the brain

At an excitatory chemical synapse between two neurons

there is increased permeability of the postsynaptic cell to both Na+and K+

Presynaptic facilitation by serotonin is caused by

calcium channels in the presynaptic membrane remaining open longer

simple diffusion

movement of a solute from an area of high concentration to an area of low concentration

membranes slow or speed up diffusion

- slow

- The major factor limiting diffusion is the hydrophobic interior of its lipid bilayer.

examples of non-polar - rapid diffusion

- Oxygen, carbon dioxide, fatty acids, and steroid hormones are examples of nonpolar

molecules that diffuse rapidly through the lipid portions of membranes.

What easily diffuses through the lipid

- Lipophilic (lipid-loving) substances diffuse easily through lipid bilayers, whereas polar

molecules and other hydrophilic (water-loving) substances do not.

osmosis

Diffusion of water through a selectively permeable membrane

- high to low concentration

Osmosis is mediated via

aquaporins ( important in the kidney, permeability flux is dependent from cell to cell)

osmolarity

total solute concentration of a solution

One osmol ....

is equal to 1 mole of solute particles.

higher the osmolarity

lower the water concentration

greater the osmotic pressure

isotonic solution

a solution whose solute concentration is equal to the solute concentration inside a cell

hypertonic solution

A solution in which the concentration of solutes is greater than that of the cell that resides in the solution

hypotonic solution

A solution in which the concentration of solutes is less than that of the cell that resides in the solution

Describe the distribution of calcium across a (muscle) cell

membrane and why this distribution is critical so muscle can

contract.

In resting muscle, calcium (Ca2+cap C a raised to the 2 plus power

𝐶𝑎2+) is heavily concentrated inside the sarcoplasmic reticulum (SR) and kept at very low levels in the cytoplasm (sarcoplasm) via ATP-driven pumps. During contraction, an action potential triggers the rapid release of this stored calcium into the cytoplasm, initiating contraction, before it is pumped back to the SR

Muscular tissue

- made of myofibrils -> read more and study the process lecture 3

Sacromere

Basic contracting unit of muscle cell consits of actin and myosin filaments between z-lines in a muscle cell

3 major steps in making a muscle move

1. Excitation

2. EC coupling

3. Contraction

Excitation of muscle fiber

1.) arrival of nerve signal

2.) acetylcholine (ACh) release

3.) binding of ACh to receptor

4.) opening of ligand-regulated ion gate; creation of end-plate potential

5.) opening of voltage-regulated ion gates; creation of action potentials

EC coupling

EPPs at end plate sum and result in action potential. this propagates into T-tubules

2) DHP-Receptors notice change in potential. This results in opening RyR ( opening it) -- this is a Ca release channel

3) Ca moves down its gradient, out of the smooth reticulum and into the muscle cytoplasm

4) Ca binds to troponin, prepares muscle for contraction

Rough Endoplasmic Reticulum

An endomembrane system covered with ribosomes where many proteins for transport are assembled.

Smooth Endoplasmic Reticulum

An endomembrane system where lipids are synthesized, calcium levels are regulated, and toxic substances are broken down.

In order for actin and myosin to be able to carry out their function, ______________ must first rush into the cell to remove the molecule that normally blocks them from grabbing and sliding across each other.

ADP+Pi to bind

ADP= unbind

For muscle contraction to occur ATP+Pi must bind to where

the myosin head

Excitation of muscle

Initiated in the neuromuscular junction of the sarcolemma, where an action potential from the nerve transmits an action potential to the muscle ( READ MORE)

How the muscle physically moves CONTRACTION

1)ADP+Pi attached to myosin -- this is the "energized" cross bridge

2) Binds to actin, now this is "crowded" so the release of ADP+Pi -- THIS IS THE POWER STROKE

3) Myosin + actin ??? read more im confused

4) myosin+ atp, dissociate from actin

5) Mysoin +atp (RATE LIMITING STEP)

: ATP hydrolysis by myosin ATPase

Players in EC Coupling

- endplate -- ligand gated ion channels on muscle cell

- T- tubles

- DHP receptors, on cell membrane ( charge sensitive)

-Sarcoplasmic reticulum ( stores Ca)

- Ryanodine receptor (Ryr-- Ca release channel

Rigor

Actin and myosin cant separate due to no ATP being made

events in relaxation of a muscle

What do organophosphates ( insecticides) do?

- Blocks AchE receptor sites by binding to them

- DEATH OF PARALYSIS

- depolarizing block of Ach doesn't get broken down, meaning constant contraction

- Muscle cell AP is stuck in depolarizing

Vecuronium

- Paralytic agent

-Ach atagonist

: blocks Ach from binding to the nicotinic R, so cells don't get EPP

- AP stuck at threshold " depolarizing block"

Parkinson's disease

- degeneration of dopamine- releasing neurons of SUBSTANTIA NIGRA

- BASAL NUCLEI deprived of dopamine becomme overreactive, results in tremors

- unemotional appearance, shuffling gait, bad posture

Dopaminergic Agents

promote activation of dopamine receptors

cholinergic-blocking drugs

Drugs that block the action of acetylcholine and substances similar to acetylcholine at receptor sites in the synapse.

Alzheimers Disease

- degeneration of cholinergic neurons

- decreased Ach

- loss of postsynaptic neurons

- widening of the sulcus

- shrinking of the gyres

neurofibrillary tangles

- apart of alzheimers

- interefere with transport mechanisms, killing the neurons

Amyotropic Lateral Sclerosis (ALS)

-Degeneration of motor neurons in spinal

cord, brainstem, cerebral cortex

Amyotropic Lateral Sclerosis (ALS) causes

overactive microglia that

kill neurons, or buildup of oxygen-free

radicals that neurons or astrocytes cannot

counter

Amyotropic Lateral Sclerosis (ALS) symptoms

Speaking difficulties, clumsiness,

fatigue, coordination issues, muscle

twitches, weakness

• Cognitive function usually remains normal

- ex: can feel the warmth of a blanket, but can't move

Diabetic Peripheral Neuropathy

- loss of sensory neuron

- progressive loss of nerve fibers in Post and Anterior nervous system

Posterior

dorsal = back

Anterior (ventral)

front

Where does the calcium for skeletal muscle CONTRACTION come from?

Ca storgane organelle, Smooth reticulum

Where does the calcium for skeletal muscle EXCITATION come from?

- the extracellular enviroment

Relaxation of a Muscle

- no more AP from from alpha motor neuron

- AChE ( acltylcholine esterase) breaks down leftover Ach

- SR stops releasing CA, troponin no longer bound to CA

- Ca ATPase pumps, ( use ATP), pumo left over Ca2+ back into SR ( this is slow)

A hormone is transported in your bloodstream. How

does it know where to stop/act?

There are specific receptors for the hormone in the

body, and the hormone travels to those

what is the endocrine system

- duckless glands that secrete hormones or hormone secreting cells

hypothalmus gland

- apart of the endocrine system

- signals to the pituitary gland

- secretes neurohormones

- releasing hormones ( TRH) SYTHEMSISES STORED IN POSTERIOR PITUTARY

- inhibiting hormones : ( GHIH), INHIBITS ANTERIOR PITUITARY GLAND FUNCTION

Pituitary gland sides

anterior ( adenohypophysis)

posterior (neurophypophysis)

3 types of hormones

amines, peptides, steroids

Amines

Structure: derivates of tyrosine

Receptor: On plasma membranes

How does it travel in the blood: FREELY HYDROPHILIC

EXAMPLES: epinephrine ( this is an amine and a neurotransmitter), norepinephrine, Dopamine, Thyroid hormone ( intracellular receptor + needs a binding protein to travel in blood)