Electrical Excitability and the Neuronal AP Flashcards
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)
