Transmembrane potential of cardiac contractile cells versus spontaneous cardiac action potentials

Question 1

describe the origin of the resting membrane potential

Answer 1

1. at rest cardiac myocytes have a negative membrane potential of -80 to -85mV (negative inside relative to the outside)
2. made up of the weighted average of the equilibrium potentials of contributing ions
3. each ion’s weight/contribution to MP depends on how permeable the membrane is to it
4. membrane permeability to an ion is determined by if there are pathways and if those pathways are open

Question 2

at rest, what ion is the membrane most permeable to and what does this mean for RMP?

Answer 2

at rest membrane is most permeable to K+, so RMP (-80 to -85mV) is closest to K+ equilibrium potential (-90mV)

Question 3

how is the resting membrane potential established?

Answer 3

1. Na+/K+ ATPase pumps 3 Na+ out and 2 K+ in, an energy dependent process that sets up a net positive charge outside the cell as there is more K+ moving in than moving out
2. K+ moves out of the cell along its concentration gradient through the open K+ channels and unopposed negative ions are left behind on the inner surface of the membrane
3. this causes a net effect of negative membrane potential

Question 4

describe phase 4 of the action potential of atrial and ventricular myocytes

Answer 4

stimulation by adjacent cell reduces RMP to a critical level (threshold, -70mV)

Question 5

describe phase 0 of the action potential of atrial and ventricular myocytes

Answer 5

1. at threshold, voltage-gated fast Na+ channels suddenly open and Na+ ions rapidly flood inward down their concentration gradient
2. loss of membrane polarity (depolarization) occurs as membrane voltage moves toward (but does not reach) ENa+
3. after 1msec, Na+ channels close and remain closed until repolarization in phase 3

Question 6

describe phase 1 of the action potential of atrial and ventricular mycoytes

Answer 6

1. early repolarization as Na+ channels are closed and voltage-gated K+ channels open and K+ moves out of the cell down its concentration gradient
2. membrane potential becomes more negative, beginning repolarization BUT
3. voltage-gated L-type Ca2+ channels start to open slowly

Question 7

describe phase 2 of the action potential of atrial and ventricular myocytes

Answer 7

1. plateau phase as Ca2+ enters cell through VG L-type channels down its concentration gradient
2. Ca2+ induces more Ca2+ release from sarcoplasmic reticulum, called excitation-contraction coupling and causing the cell to contract!
3. K+ channels remain open though so K+ moving out balances Ca2+ moving in and there is no net change in membrane potential
4. plateau ends as L-type Ca2+ channels slowly close

Question 8

describe phase 3 of action potential of atrial and ventricular myocytes

Answer 8

1. final repolarization as L-type Ca2+ channels are closed and K+ moves out of cell unopposed, allowing membrane to completely repolarize

Question 9

describe phase 4 of the action potential of atrial and ventricular myocytes in the context of restoration of ion balance/resting MP

Answer 9

1. Na+/K+ ATPase pump restores concentration gradients necessary for next beat
2. Ca2+ is pumped out of the cell via the Ca2+/Na+ antiporter
3. and then of course stimulation by adjacent cell reduced RMP to threshold to start all over again

Question 9

compare and contrast non-automatic cells versus automatic/pacemaker cells (3)

Answer 9

1. non-auto are atrial/ventricular myocytes auto are SA, AV and purkinje fibers
2. non-auto depolarize ONLY in response to external stimulation, while auto can depolarize independently of external stimulation
3. non-auto have a stable, flat phase 4 of AP while auto have an unstable phase 4 from inward leak of Na+ and Ca2+ ions causing spontaneous depolarization

Question 9

describe the general alterations to the phases of the AP for pacemaker cells (5)

Answer 9

1. RMP is less negative of pacemaker cells since membrane less permeable to K+
2. phase 4 is unstable
3. threshold potential is less negative
4. phase 0 has a slower upstroke
5. no plateau phase, repolarization is more gradual

Question 10

describe phase 4 of SA and AV pacemaker cells

Answer 10

1. at rest cells are less permeable to K+ than contractile cells so the RMP is less negative
2. spontaneous phase 4 depolarization (gradual slope) due to slow inward leak of Na+ and Ca2+ thanks mainly to HCN (funny channels, Na+) and T-type (transient) Ca2+ channels

Question 11

describe phase 0 of SA and AV pacemaker cells

Answer 11

1. spontaneous depolarization as membrane potential “drifts upward” until threshold is reached
2. at threshold, VG L-type Ca2= channels open to slowly generate action potential (pacemaker cells do NOT contain fast Na+ channels)
3. Ca2+ moves into the cell causing depolarization

Question 12

describe phase 3 of SA and AV pacemaker cells (there is no phase 1 or 2)

Answer 12

1. repolarization as K+ channels open and K+ moves out of cell
2. negative MP is restored

Question 13

what 2 mechanisms can modify the rate of impulse formation (HR) in the normal heart?

Answer 13

1. changing the rate/slope of phase 4 depolarization (steeper slope = faster HR, flatter slope = slower HR)
2. change phase 4 starting point/max negative potential; hyperpolarization/downshift means it takes longer to reach threshold = slower HR

Question 14

describe what influences the mechanisms that modify HR

Answer 14

the autonomic nervous system

sympathetic activation: increases Na+ and Ca2+ leak channels to increase slope of phase 4 (faster HR)

parasympathetic activation: decreases Na+ and Ca2+ leak to decrease phase 4 slope and increase K+ permeability to hyperpolarize cell (slower HR)

Question 15

describe pacemaker hierarchy

Answer 15

SA node is the major pacemaker and has the fastest intrinsic rate of depolarization, followed by AV node, then by purkinje fibers

Question 16

describe the concept of ectopic foci/pacemakers

Answer 16

regions other than SA node can initiate betas in special circumstances such as:
1. if the activity of a higher-order pacemaker is depressed (failsafe)
2. if the communication between higher-order pacemakers and the rest of the heart are blocked (failsafe)
3. if automaticity becomes enhanced or a non-auto cell develops abnormal automaticity and fires while normal pacemaking is still functional (BAD)

Question 17

compare and contrast atrial/ventricular mycoytes, SA and AV nodal cells, and purkinje fiber cells (5)

Answer 17

1. myocytes are contractile, SA and AV nodal and purkinje are myoconductive
2. myocytes can only depolarize in response to external stimulation, the others can depolarize independently of external stimulation
3. myocytes and purkinje fibers have a RMP of -80 to -85 while SA and AV nodal cells have RMP of -60mV
4. mycocytes have a stable phase 4, SA and AV nodal and purkinje fibers have an unstable phase 4 due to inward leak of Na+ and Ca2+
5. myocytes and purkinje fibers have a rapid phase 0/fast response thanks to fast Na+ channels, while SA and AV nodal cells have a slow phase 0/slow response due to lack of fast Na+ channels and presence of L-type Ca2+ channels