Electrical Excitability and the Neuronal AP Flashcards Preview

FHB I - Cardiac Unit > Electrical Excitability and the Neuronal AP > Flashcards

Flashcards in Electrical Excitability and the Neuronal AP Deck (26):

Describe the shape (configuration) of neuronal, skeletal and cardiac action potentials.

-all have upstroke, and repol. main diff is duration.

-duration of AP is diff. motor neuron is less than 2 milli-sec long. skeletal muscle similar to nerve AP (couple milliseconds long) cardiac AP is 300-400 milliseconds long


Why does the heart have a long AP?

bc protects heart. cannot be reactivated in rapid way. 60 or 70 beats per minute. 1000 milliseconds between beats and your heart has to contract during that time so electrical activity is long in order to protect heart from additional electrical activity that may arise.


Draw and label a graph of the response of the membrane potential of an axon to increasing pulses of depolarizing current.

Describe what happens at each stage.

how does AP get initiated in nerve? dashed line- resting membrane potential. impulse comes along and propagates or conducts or in CNS it arises from neurotransmitter releases. generates sub-threshold depolarization. when get to critical level, large enough stimulus (top one) then you can hit threshold which is tipping point

threshold-(point where inward current overcomes outward current) basically sodium channels open up and because of gradient of Na across membrane…more sodium outside in bloodstream than cells there's driving force for Na to go into cell and the only thing preventing Na from going into cell is the permeability of the cell but when you hit threshold you hit a tipping point at which inward Na current exceeds outward K current. K going out makes membrane more negative. Na moving in makes membrane more positive. want to activate the upstroke so when get to threshold it activates critical number of Na channels and they open very rapidly and Na can rush in. drives membrane potential to equilibrium potential for Na -very positive value.

K opens up and this drives membrane back down to K equilibrium potential.
How does AP become initiated?
sub-threshold depolarizations if large enough reach the threshold for Na channel open it up and cause AP to be initiated
in nerve also have repolarization that doesn't go back to RP it undershoots it and is referred to after hyper-polarization or hyper polarizing after potential and thats because the membrane potential is going to equilibrium potential for K which is way down here and that drives it a little more negative.


Describe the upstroke of an AP.

upstroke of AP is due to Na channel turning on. outside of cell has more Na than inside so gradient of Na to flow down cell passively. as soon as permeability of channel opens Na flows down into cell (down its chemical and electrical gradient- large driving force of Na into cell) depolarization continue until equil. potential for sodium. so if Na were allowed to continue to flow into the cell, the inside of cell would become so positive that it prevent further flow of Na down its conc. gradient and cell would be in equilibrium at ENa. (drives toward ENa but never gets there) when membrane becomes permeable to ion, it drives membrane potential toward equil. potential for that ion. Na flowing in, inside of cell more positive,


What happens to the Na and K channels as the cell depolarizes?

depolarization opens up K channels which open very slowly. gating characteristics much slower. Na much larger in amplitude and much more rapid than K channel
important with Na channel- when it depolarizes the membrane potential this depolarization turns off Na channel and inactivates it. voltage of cell becoming positive actually turns off Na channel if that didn’t happen then voltage of cell would be positive forever.


What does the dog frog toxin do?

frog toxins that if frog bites you can toxin prevent inactivate gate from inactivating. so when cell depolarizes it stays depolarizes and you die. good way to kill someone if you wanted to. poisonous frogs do this. dog frogs.


What causes repolarization?

inactivation gate turns off Na channel bc at same time that outward current is being generated by K conductance -generating depolarization need to turn off Na channel and turn on K channel and that causes repolarization. bc membrane becoming more permeable to K -so K leaving cell, inside cell becoming more negative.. back to RP.. going toward point that if you allowed it it would become so negative inside that K wouldn't be allowed to leave (driving it toward EK) when membrane potential permeable to ion it drives the voltage toward equil. potential for that ion.


Describe the flow of Na/K along their gradients. Why is there an imbalance between ions across the membrane?

all passive - as soon as Na channel opens, Na rushes in down it chemical and electrical gradient passively no energy involved. When K channels open K flows passively out of cell because more K inside the cell than outside the cell and causes membrane to re-polarize. ion changes are all passive, no energy involved

why imbalance between ions across membrane? Na/K pump…metabolic pump runs off ATP and it maintains the balance of ions. it generates a battery- more charge on one side than other so when channels open up ions flow. all runs off ATP.


Describe the m and h Na gates at rest, depolarization, and the inactivate state.

at resting conditions m gate closed, h gate opens and sitting at -90 millimols. little Na leaks in. when cell hits threshold at critical point when Na channel opens, membrane depolarizes, opens up m gate, m gate allows Na to flow in, membrane becomes more positive opening up more Na channels and have regenerative depolariztion- positive feedback.

positive feedback occurs. so m gate opens v rapidly. h gate starts to close and relative to m gate it closes rel. slowly. for a moment both gates are open and thats when Na flows in and thats when upstroke of AP occurs over half a millisecond.

if maintain depolarization with Na channel the h gate snaps closed. depolarization that has closed the h gate. at that moment m gate open and h closed and this is peak of AP, inactivation state. no more Na flowing in. so Na conductance is 0. h gate inactivates or closes positive voltages. both m and h sensitive to voltage but h gate closes on depolarization

get to inactivated state to resting state to get another AP. recovery from activation. cell must repolarize. thats where restores Na channel back to resting state and opens h gate and closes m gate. opening of K channel causes repolarization. that REpolarization back down to rest restores Na channel characteristics back down to rest.


What do anti-arrhythmic drugs do?

anti-arrhythmic (class I) drugs block cardiac arrhythmias by binding to Na channel at certain stages of this cycle. certain drugs bind more effectively to inactivated channel, resting channel or activated channel. others prevent reactivation of channel.

Class 3 and Class 1 anti-arrythmic drugs designed to lengthen refractory period of heart to prevent tapacardia -rapid impulses from going around the heart.


What are Na gating kinetics dependent upon?

both time and voltage


Describe regenerative depolarization.

Na+ moves rapidly into the cell down both its electrical and concentration gradients to depolarize the membrane potential toward ENa. Depolarization increases Na+ permeability (open more Na+ channels) which in turn causes further depolarization (positive feedback).


What is the basis for refractory periods?

The voltage-dependent inactivation of Na+ channels is the basis for refractory periods.


Draw and describe the graph voltage dependence of Na channels (number of Na channels on y axis and membrane potential on x axis)
What are the clinical implications of this graph?

100 percent (1) Na channels are available. at resting state m closed, h open. can form AP when hit threshold. as voltage of RP becomes more positive… the number of Na channels falls off bc h gate senses more positive voltage and its closing. millions of Na channels in membrane and its probability situation. at say, -60, 50 percent of Na channels closed, 50 percent still open. at -60 millimols 50 percent of channels have h gates closed. at -50 millimols almost 100 percent of these channels are closed down, almost all h gates closed.

many pathological situations where RP of nerves and hearts become more positive…Na channels available will go DOWN in this situation. goes down in hurry. very sensitive to voltage over narrow voltage range. without Na channels don't have upstroke of AP. and with only 50 percent of Na channels available, would conduct only very slowly. Na that comes in during upstroke of AP that causes depolarization of next segment of membrane. Na upstroke which is stimulus for conduction. so if lose Na channels slow conduction dramatically so get muscle weakness bc can't activate skeletal muscles… troubles thinking- can’t integrate information bc NS not working properly. in heart can go into fatal arrhythmia… this relationship applies to all excitable tissues that use Na in AP.


Describe the difference between absolute and relative refractory periods.

Absolute refractory period: The TIME during which a stimulus cannot elicit a regenerative response, i.e. action potential.

Relative refractory period: The TIME during which a stimulus can elicit a regenerative response, i.e. action potential.

In nerve (and heart), refractory periods are based on the voltage-dependent characteristics of Na+ channels. At more positive voltages, Na+ channels inactivate or become unavailable for activation (absolute refractory period). As the membrane potential repolarizes, Na+ channels recover from inactivation (relative refractory period).

(any time cell depolarizes this whole area is absolute refractory. when cell gets more negative down here on final repolarization it starts to go from inactivated back to activated state. percentage of channels starting to recover activation. h gates starting to open again. relative refractory period- COULD get a stimulus and generate AP but need strong stimulus)


What causes the activation/opening and deactivation/closing of K channels?

Depolarization of the action potential upstroke activates the opening of K+ channels causing K+ to flow out of the cell, down its concentration gradient.

Outward K+ current repolarizes membrane potential back toward EK and causes the membrane potential to go more negative than RMP, i.e. hyperpolarizing afterpotential.

K+ channels deactivate when the membrane repolarizes (no inactivation parameter).


Describe some key differences between Na and K channels.

unlike Na channels K channels remain open with maintained depolarization

do not turn off on own. do not have inactivation gate.
if you depolarize membrane and open K channel and hold depolarization, K channel will stay open unlike Na channel.

no h gate. just opens. only thing that closes it is if the membrane REpolarizes and that closes it. one gate that opens and closes.

turning off K channel also turned off by REpolarization

Voltage-dependent activation of K+ channels is much slower than activation of Na+ channels.


Describe hyperkalemia.

hyperkalemia- high K. normal extracellular K is somewhere between 3-5 millimolar (KNOW!) anything higher than 5 is hyperkalemia, anything lower than 3 is hypokalemia

Nerst eq.- predicts that RMP becomes more positive as extracellular K increases, as extracellular K increases, it reduces the driving force that allows K to leave cell. K normally leaks out of cell. if raise extracellular K then less K will leak out. inside of cell retains more K, becomes more positive. and resting membrane potential becomes more positive. inside of cell has 150 millimolar K, outside has 4 millimolar. if extracellular K goes up by 2 from 4 to 6 that is a 50 percent increase in K concentration and has a dramatic effect on resting potential.

how does K change? renal failure. (allows K to elevate too much) pt on dialysis go on dialysis among other things to keep K low.
-as RP becomes more positive, Na channels less available bc of h gate inactivation, decreases conduction and get signs and symptoms of slow muscles. and can die of hyperkalemia. this is what inject in death row pt. cocktail is partly high K-depolarize heart and put in high arrhythmia or ventricular fibrillation


How does Ca modulate Na channel activity?

Ca modulates Na channel activity by alternating membrane surface charge … proteins have negative charges on outside of membrane. blood has divalent cations in form of Ca. most of bound Ca bound to proteins. ion portion too that you usually measure in patients…not bound to anything.

if Ca concentration goes up or down the amount bound to proteins changes. equilibrium. bound Ca bound to proteins. when Ca bound to proteins changes…changes surface charge (charge on protein..doesn’t change resting potential of heart or nerves) but Na channel is a protein. so when Ca binds to protein surrounding Na channel, Na channel thinks its in a more positive environment. so h gate starts to close. even though membrane potential is no different.. environment around Na channel more positive bc of binding of Ca to negative surface charges so some Na channels come inactivated.


Describe hypercalcemia. How would you recognize this condition in a patient?

Hypercalcemia- when Ca binds to Na channel surface charge, the H gate starts to close, less Na channels available…so have raised threshold. if less Na channels available makes it more difficult for membrane to initiate an AP . have raised threshold. reduced membrane excitability.

how do you know this in a patient? how do you know membrane excitability has been reduced? physical diagnosis with noninvasive methods. functional reason they have a decrease. measure reflexes. red hammer. reflex on knee, jaw, elbow, if they have muted or attenuated reflexes then you might think they have low membrane excitability and take blood test and see if Ca is responsible. when you find high calcium you have to figure out what’s causing the high calcium - could be tumor or a lot of different things.


Describe hyperventilation and hypoventilation.

Hyperventilation - blow off CO2 - respiratory alkalosis - decrease free plasma Ca2+ concentration - increase neuronal membrane excitability.

Hypoventilation - accumulate CO2 - respiratory acidosis – increase free plasma Ca2+ concentration – decrease neuronal membrane excitability.


Define length space constant.

Length (Space) constant (λ): the distance over which a subthreshold depolarization (local response) will spread and influence the next segment of membrane. The longer the space constant, the more rapid is conduction.

It is the distance over which a subthreshold depolarization (local response) will spread and influence the next segment of membrane. The longer the space constant, the more rapid is conduction bc you influence larger amount of membrane to be depolarizes as AP conducts.

this sub threshold depolarization dying out. dies out exponentially. shown in red. dies to 0 exponentially. when decays to 37% of its size…that distance is one space constant. for smaller axon decays more rapidly so decays over shorter distance so has a smaller space constant. so large axons have large space constant and small axons have short space constant. thats reason why large axon conducts more rapidly than a small bc that sub threshold depolarziation which initiates AP dies out v quickly in small axon but in large axon can influence large amount of membrane and cause the AP to conduct v rapidly.
so space constant is fundamental property of axon- measurement of how easily an axon can carry electrical activity.


What does myelination do to an axon? (What 2 factors determine space constant?)

myeleinate axon- make space constant longer. thats why nerves conduct rapidly. reason why have space constant bc there is a certain amount of resistance. has internal resistance. in large axon internal resistance is low. in small axon internal resistance is quite high. so naturally current decays less if resistance is low and decays rapidly if resistance is high. current is injected into this axon (positive charge causing depolarization) positive charge propagates or spreads internally it also forces current to flow out. losing charge all the time because as the inside of cell becomes more positive it forces potassium out of channel and lose K over distance.

so 2 factors determine space constant - membrane resistance (how easy it is for current to leave membrane) and internal resistance (flow of current down axon) ratio between membrane and internal resistance. idea of space constant- distance over which current decays will determine how rapid AP conducts. longer space constant= more rapid conduction; the smaller the constant, the slower the conduction


What does the myelin sheath do? How?
Describe how this relates to saltatory conduction.
(What is concentrated at nodes of Ranvier?)

what does it do? dramatically lengthens space constant. why? bc current cannot leak out of cell through K channels. not only current flowing down axon but also current leaking out K channels. but hose K channels now covered up by myelin, so resistance has gone up meaning that K cannot leak out and now all K or positive charge forced down axon through internal resistance.

myelin sheath increases membrane resistance by covering up K channels and therefore increases length constant of axon. significantly increases conduction velocity. distance between nodes is 1-2 millimeters. which means space constant has to be at least that long to have impulse spread from node to node. increased space constant so impulse can spread between these nodes - so only place get AP is right at node. only place Na channels is at nodes and thats why you get AP there - Na channels concentrated at node of Ranvier. AP only occur at nodes and therefore appear to jump from node to node (what saltatory means) reality is there is electrical activity conducting through this membrane w v long space constant. the sub threshold depolarization is conducting all along this membrane and its still strong enough to bring membrane to threshold at this node generating an AP - this AP brings inward current and generates sub threshold depolarization which spreads impulse to next node. so AP appears to jump from node to node quickly


Describe MS.

MS - destroy myelin sheath bc space constant has been reduced and impulse cannot propagate to the node. if the myelin sheath taken off, K leaks out and this reduces local response to the point where space constant isn't long enough to reach the node. so the space constant is really determining conduction in these situations. as disease progresses the symptoms progress and eventually pt. cannot breathe and die from MS. not all. depends on severity. whole basis of demyelinating diseases=the space constant. NO Na channels under the myelin. when myelin is gone the only thing is K channels.


Compare EPSP and IPSP in regards to neurotransmitter release, ion influx, membrane potential change, and probability of firing an AP.

neurotransmitter release- excitatory (Ach, glutamate)
ion influx- cation (Na in, K out)
membrane potential change- toward Ena/K OmV
probability of firing AP- increase

neurotransmitter release- inhibitory (GABA, glycine)
ion influx- anion (Cl in)
membrane potential change- toward E Cl -65mV
probability of firing an AP- decrease