Chapter 2 Flashcards
How is the electrical potential measured in an individual cell?
mV
Define resting membrane potential (Em).
The electrical potential across the cell membrane. Dependent on concentration of ions, relative permeability of ions and the ionic pumps which transport ions across the membrane.
What is the single most important ion involved with determining the membrane potential?
K+: high inside, low outside
What are the intracellular and extracellular concentrations of K+, Na+, and Ca++ in a typical cardiomyocyte at a resting membrane potential of -90Mv?
K+: Intra 150mM/ Extra 4mM
Na+: Intra 20mM/ Extra 145mM
Ca++: Intra 0.0001mM/ 2.5mM
What is a chemical gradient?
A difference in the concentration of chemicals across a membrane,
What are the intracellular and extracellular concentrations of K+, Na+, and Ca++ in a typical cardiomyocyte at a resting membrane potential of -90Mv?
K+: 150 mM in/ 4 mM out
Na+: 20 mM in/ 145 mM out
Ca++: 0.0001 mM in/ 2.5mM out
What is a chemical gradient?
A difference in the concentration of chemicals across a membrane.
The concentration differences across the cell membrane for these ions are determined by what?
1) the activity of energy-dependent ionic pumps
2) the presence of impermeable, negatively charged proteins within the cell
Explain how concentration gradients of ions across a cell membrane affect membrane potential.
Due to concentration gradients of ions, the ions flow from high to low concentrations. This creates a desire to flow towards lower concentrations, which means that the ions want to leave their current location. For K+, they leave behind negatively charged proteins which leaves the membrane potential more negative, if other ions aren’t balancing it out.
What is an equilibrium potential?
The equilibrium potential is the difference across the membrane which is required to maintain the concentration gradient. For example: it is the potential necessary to oppose outward flow of K+ down the concentration gradient. With equilibrium potential being -96mV, and Em of a ventricular myocyte being -90mV, as K+ potential reaches -90mV, it will stop wanting to diffuse out.
What is the equilibrium potential for K+?
-96mV.
Define net electrochemical force
Net electrochemical force is the difference between the resting membrane potential and the equilibrium potential for that specific ion.
Net Electrochemical force= Em - Equilibrium potential
For Na+, the resting membrane potential is 52mV, while the v. myocyte is -90mV. This means that the cell interior has to reach 52mV for Na+ to stop wanting to diffuse inward. This creates a large net electrochemical force of -142mV for Na+.
If the Em = -90mV, what is the net electrochemical driving force for K+?
+6mV. Relative permeability of K+ at rest is high, but there is only +6mV of electrochemical force leading to slow leak of K+ out. Because K+ is highly permeable at rest, it has greater influence on resting membrane potential(-90mV).
What is the equilibrium potential for Na+?
+52mV
If the Em = -90mV, what is the net electrochemical driving force for Na+?
-142mV=(-90-(+52)
What is the equilibrium potential for Ca++?
+134mV
If the Em = -90mV, what is the net electrochemical driving force for Ca++?
-224mv=(-90-(+134)
Explain how the electrical and chemical forces work collectively to determine the movement of ions.
The resting membrane potential is a product of:
1) the concentration gradient(chemical force) of ions and
2) the relative permeability of each ion(the movement of an ion being driven by a net electrochemical force).
If the membrane has greater permeability to one ion over another, that ion will have greater influence in determining the membrane potential
Why would there be little movement of and ion even when there is a large electrochemical force acting on the ion?
There may not be a concentration gradient due to concentration of ions being similar both intra and extra cellular
What is ion conductance?
Ion conductance is the ion current divided by the net electrochemical force acting upon that ion.
ion current/net electrochemical force
How are ion permeability and conductance related?
An increase in the permeability for an ion results in an increase in the ion conductance.
Write an equation that relates Em to the relative conductances and equilibrium potentials of K+, Na+, and Ca++.
Em=g’K(Ek) + g’Na(Ena) + g’Ca(Eca)
This represents the sum of individual equilibrium potentials each multiplied by the membrane conductance(g’)
In a cardiac cell, how much do the individual ion concentrations change when ions cross the cell membrane during depolarization and repolarization?
Very little
Why is the Em close to the EK?
because g’K+ is high in resting cells
Why do Na+ and Ca++ contribute little to the resting membrane potential?
The low relative conductances of Na+ and Ca++ are multiplied by their equilibrium potential values causing those ions to contribute little to the resting membrane potential
How do changes in conductance of the different ions change the membrane potential, such as during an action potential?
When conductance changes, the membrane potential reflects a change in mV. For example, during an AP, the membrane potential gets less negative due to increased permeability of Na+, allowing for more + ions inside and making the membrane potential less negative.
How is the conductance of some ion channels influenced by the concentration of the ion?
A decrease in concentration would reduce ion conductance. If concentration influences the desire to cross the membrane, a lower desire would result in less conductance.
With an action potential, in general, how many ions move across the sarcolemmal membrane?
small, relative to the total number of ions
Diagram, describe, and explain in detail the sarcolemmal ion pumps and exchangers
Na+/K+ ATPase: 3:2 change utilizing ATP to pump. 3 Na+ exit and 1 K+ enters.
Na+/Ca++ Exchanger: 3:1 exchange based off of Na concentration gradient. 3 Na+ enter and 1 Ca++ exits.
ATP dependent Ca++ pump: Remove Ca++ from cell using ATP.
Which of these requires ATP in order to function?
Na+/K+ ATPase and ATP dependent Ca++ pump
Define the term electrogenic
Electrogenic is the creation of a + or - charge based of exchange of ions
For example: 3 Na+ exit the cell and 2 K+ enter, leaving a more negative potential, due to 3:2 exchange.
What are the two general types of ion channels?
Voltage-gated ion channels respond to a threshold voltage being met
Receptor-gated ion channels response to chemical signals operating through membrane receptors
Diagram and describe the general structure of sodium channels in cardiomyocytes.
Two gates regulate movement of ions through the channel. At rest, the M gate(activation gate) is closed and H gate(inactivation gate) is open. The structures making the channel up are polypeptides which undergo conformation changes in response to voltage change.
What are the 3 primary states of the fast sodium channel?
Resting(M gate closed), Activated(open) and Inactivated(H gate closed)
Explain the transition between each state and the factors that contribute to these transitions.
When M gates are activated by voltage change during depolarization, they open, allowing Na+ to rush in due to its concentration gradient of low intra/ high extracellular concentrations.
As the M gates open, the H gates begin closing. M gates open much faster than the H gates close. This allows a small timeframe for Na+ to enter.
When H gates close, the cease the Na+ flooding in.
The inactivated-closed state persists as the membrane potential re-polarizes.
Near the end of re-polarization, the M gates close and H gates open, which is the resting position.
How would the fast sodium channel response change when the resting membrane potential is partially depolarized or slowly depolarized?
Partial depolarization inactivates Na channels by closing the H gates.
The more depolarized, the more inactivation occurs. At -55mV, all fast Na+ channels are inactivated.
What factors determine the amount of sodium that passes through sodium channels when a cardiac cell undergoes depolarization?
the number of Na channels
the duration which the Na channels are open
the electrochemical gradient driving Na+ inwards
What is an action potential?
Sudden depolarization of the membrane followed by repolarization
What is the action potential duration in a typical ventricular cardiac myocyte, and how does this compare to other muscles and nerves?
Cardiac: 200-400 ms
Nerve: 1-2 ms
Skeletal: 2-5 ms
Draw the “fast response” action potential and label each of the phases.
Five phases:
4: Resting
0: Rapid depolarization
1: Initial repolarization
2: Plateau
3: Repolarization
4: Resting
What cell types exhibit the “fast response” action potential?
Non-pacemaker cells
Do non pacemaker cells have a true resting membrane potential?
Yes, near equilibrium potential for K+
Is K+ conductance relatively high or low during phase 4, phase 0, phase 1, phase 2, and phase 3 of the fast cardiac action potential?
K+ has an inverse relationship with the fast AP. Therefore, K+ conductance is very high during phase 4, but drops during phase 0 and starts to get higher during phases 1, 2 and 3 until very high again at phase 4.
Is Na+ conductance relatively high or low during phase 4, phase 0, phase 1, phase 2, and phase 3 of the fast cardiac action potential?
Na+ conductance is low for phase 4, but spikes during phase 0, followed by great decrease at phase 1. Na+ conductance returns to very low after phase 1 and remains there until the next phase 0.
Is Ca++ conductance relatively high or low during phase 4, phase 0, phase 1, phase 2, and phase 3 of the fast cardiac action potential?
Ca++ conductance is relatively low during phase 4 and 0, but increases during phase 1 and reaches a peak during phase 2 which slowly decrements down to low by phase 4.
Define phase 4 and describe in detail the events that are involved with this phase.
Phase 4 is the resting state. A slow leaking of K+ happens due to low net electrochemical force and high permeability of K+ at rest.
Define phase 0 and describe in detail the events that are involved with this phase.
As the membrane potential reaches -70mV(from -90mV) a threshold is reached causing rapid depolarization. This is due to voltage gated Na+ channels opening up which increases Na+ conductance. At the same time, K+ conductance falls. These changes move the membrane potential towards the Na+ equilibrium potential(+52mV).
Define phase 1 and describe in detail the events that are involved with this phase.
Phase 1 is the initial repolarization. This move towards a more negative membrane potential is due to the inactivation of Na+ channels and activation of K+ channels.
Define phase 2 and describe in detail the events that are involved with this phase.
Phase 2 is the plateau phase. This is due to both K+ channels and Ca++ channels being open. The Ca++ channel is L-type(long lasting) and opens when reaching a threshold of -40mV.
Define phase 3 and describe in detail the events that are involved with this phase.
Phase 3 is repolarization phase. K+ conductance increases due to delayed rectifier K+ channels and Ca++ conductance decreases due to permeability decrease.
What is the absolute refractory period?
During phases 0, 1, 2 and part of 3, the cell membrane is unexcitable to new AP. Does not produce a new AP because H gates are still closed.
What is the purpose/benefit of the absolute refractory period?
Limits frequency of AP that the heart can generate.
What is the relative refractory period?
A time during the end of the absolute refractory period which suprathreshold depolarization stimuli can elicit an AP
Do pacemaker cells have a true resting membrane potential?
No
What cell types exhibit the “slow response” action potential and where are they located? What is overdrive suppression and what mechanisms are involved with this?
pacemaker cells
Located in Sinoatrial Node, Atrioventricular Node and Bundle of His.
Overdrive suppression is the higher rate of the SA node suppressing the use of AV node or BoH. It doesn’t allow them to fire before the AV signal reaches them.
Define phase 4 in a PM cell and describe in detail the events that are involved with this phase.
Phase 4 is the resting.
1) Early in phase 4, gK+ is still declining.
2) A “funny” current has slow inward Na+.
3) During the second half of phase 4, there is a small increase in gCa++ through T-type Ca++ channels. These open briefly at very negative potentials.
4) As depolarization starts to reach threshold, L-type Ca ++ channels begin to open, increase gCa++ until phase 0 is initiated(threshold met).
Define phase 0 in a PM cell and describe in detail the events that are involved with this phase.
Phase 0 is the depolarization. Primarily due to increased Ca++ conductance through the L-type Ca channels(voltage-gated) which open around -40mV. The rate of depolarization is slower due to slower conduction of Ca. At the same time, a decrease in gK+ happens to further depolarization.
Define phase 3 in a PM cell and describe in detail the events that are involved with this phase.
Phase 3 is the repolarization via delayed rectifier K+ channels opening, which increases gK+ towards the Em of K+(-96mV). Ca++ channels which opened during phase 0 close, reducing Ca++ inward flow and gCa++. Phase 3 ends when membrane potential reaches -65mV.
Is K+ conductance relatively high or low during phase 4, phase 0, phase 1, phase 2, and phase 3 of the fast cardiac action potential?
K+ conductance is relatively high during phase 3 only. It starts to dip around phase 0, followed by an increase during 3 and back down to baseline(relatively low) for 4
Is Ca++ conductance relatively high or low during phase 4, phase 0, phase 1, phase 2, and phase 3 of the fast cardiac action potential?
Ca++ conductance is relatively low during phase 4, followed by a sharp increase during phase 0 and down to baseline during phase 3
Explain the pacemaker current.
The pacemaker or funny current is a slow inward movement of Na+
What is the intrinsic depolarization rate of the SA node?
100-110
What is vagal tone and when is it most active?
When vagal influences are dominant over sympathetic.
Most active at low resting heart rates
How do autonomic nerves alter SA node firing rate?
decrease vagal tone and increase sympathetic activity of SA
Define positive chronotropy and negative chronotropy.
Positive chronotropy is an increase in HR
Negative chronotropy is a decrease in HR
What are the mechanisms by which autonomic nerves alter the rate of pacemaker firing?
Change the slope of phase 4
Alter threshold voltage for triggering phase 0
Alter degree of hyperpolarization at end of phase 3
How could these mechanisms increase or decrease the slope of phase 4?
Inhibition of “funny” or pacemaker currents(slow inward Na+)
Explain the signal transduction pathway by which sympathetic activation elicits a positive inotropic effect.
Adrenergic nerves release norepinephrine which binds to B-Adrenoceptors coupled to a stimulatory G-protein which activates Adenylyl Cyclase and increases cyclic adenosin monophosphate(cAMP) which increases “funny” currents and causes earlier opeining of L-type Ca++ channels resulting in quicker depolarization and faster rate.
What neurotransmitter is released by the vagus nerve at the SA node?
ACH
What is the effect of vagal stimulation at the SA node?
Decreases slope of “funny” currents, hyperpolarizes the cell and increases threshold voltage req. to trigger phase 0
Explain the signal transduction pathway by which vagal activation elicits a negative inotropic effect
ACH binds to M2 receptors which reduces cAMP(via inhibitory G-protein). ACH also activates Kach channel which hyperpolarizes by increasing gK+
What nonneural mechanisms can alter pacemaker activity?
1) Circulating catecholomines cause tachy(epi/norepi)
2) Hypo/hyperthyroidism: Hypo= brady/ Hyper= tachy
3) Change in serum concentrations of ions will alter SA firing rate
4) Hypo/Hyperkalemia: Hypo= tachy/ Hyper= brady
5) Cellular hypoxia induces brady and abolition of PM activity d/t depolarization of membrane
6) Increased body temp=increased SA firing rate
