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Electrical Activity of the Heart

Page history last edited by PBworks 18 years ago

Lecture 3. Electrical Activity of the Heart

(Reading Assignment: Chapter 17 of Berne and Levy)


A.Types of cardiac action potentials:

*Fast response: atria, ventricle and Purkinje fibers

*Slow response: pacemaker cells in the right atria (sinoatrial nodal cells), A-V nodal cells

Reprinted from Principles of Physiology 3rd ed., (2000) by R.M. Berne & M.N.Levy, page 185 with permission from Elsevier.

Changes in transmembrane potential recorded from a fast response and a slow response cardiac fiber in isolated cardiac tissue immersed in an electrolyte solution.

Action potentials from a ventricular, a sinoatrial and an atrial cell. Note the different shapes. Why do you think the action potential shapes vary so much? The heart has to contract in a coordinated fashion in order to efficiently pump blood. The speed and the timing of contraction of different regions of the heart must be precisely controlled to produce such coordination. This is accomplished by having different proportions of ion channels expressed in the plasma membrane of each cell type.


Refractory period:The delayed reactivation of the sodium channels accounts for the refractoriness. The heart can not be re-excited during and immediately after the passage of an action potential. A local response can be generated but a propagated response can not be generated. Two degrees of refractoriness are commonly described:

Effective refractory period (ERP):During this period which begins with depolarization, no stimulus, whatever its magnitude, can produce a propagated action potential.

Relative refractory period (RRP):This begins after the end of effective refractory period and is the period when only stimuli that exceed the normal threshold can initiate a propagated response.

C.Ionic basis of resting membrane potential

a.Transmembrane potential dependence on extracellular [K].

Potassium and excitability: K+ plays a prominent role in excitability since the membrane potential of cells is determined largely by intracellular and extracellular K+ concentrations. The relatively high K+ permeability of the membrane sets the resting membrane potential to near the K+ equilibrium potential (-90 mV). The high resting K+ permeability at rest is due to opening of IK1 channels (inward rectifier potassium channels).


 But if you wish to understand the cellular basis for the graph above, then please read it.

What happens to the membrane potential as extracellular [K+] is changed from its normal value of 5 mM ?   As extracellular [K+] is increased, the membrane potential becomes less negative.  This is what would be predicted from the Nernst equation for K+.  At -90 mV, the electrochemical gradient for Na+ is very high and Na+ influx would be expected to be high if the Na+ channels were open.  However, Na+ influx is very low, since Na+ permeability of the membrane is very low at rest.   The small amount of Na+ influx is extruded by the sodium pump.
As extracellular [K+] is decreased, the relative permeability of Na+ increases, and the contribution of Na+ influx to the resting membrane potential becomes important.  Thus, at low [K+]o, the relative decrease in K+ permeability and the relative increase in Na+ permeability leads to the deviation of the measured Vm from that predicted by the Nernst equation for K+.

Chord conductance equation

In a resting cardiac cell bathed in solution containing 5 mM K+, gK is 100 times greater than gNa. Therefore: (substitute relative values for gK and gNa)


Vm = -90 mV (100/101) + 50 mV (1/101) = -89.1 mV + 0.5 mV = -88.6 mV


From the Nernst equation, EK = -61.5 log (140 mM/5 mM) = -89 mV


When extracellular [K] is decreased, gK is greatly reduced. For example, if the cell is now bathed in solution containing 2 mM K+, gK may now be only 10 times greater than gNa. and the Vm would be less negative:


Vm = -113 mV (10/11) + 50 mV (1/11) = -102 mV + 4.5 mV = -97.5 mV


If Nernst equation is used, EK= -61.6 log (140 mM/2 mM) = -113.5 mV

Therefore, at low extracellular K+, the measured Vm deviates from value calculated using the Nernst equation.


Decreasing extracellular K+ also starts to inhibit the Na pump. This leads to accumulation of Na+ in the cell that contributes to less negative membrane potential.

b.Importance of resting (background) K+ permeability (IK1).


IK1 is an inwardly rectifying K+ current. This means that the inward current at membrane potentials below EK is larger than the outward current at potentials above EK (EK=-90 mV).


Another important property of cardiac IK1 is that it has a negative slope in the current-voltage relationship. Thus, the outward current is smaller at depolarized potentials (i.e., at 0 mV) than the outward current close to EK. This property of IK1 is important in shaping the cardiac action potential as discussed below.


In cardiac cells, K+ always moves OUT of the cell when K+ channels are open. The inward current observed at potentials below EK would never be observed under physiological conditions, as membrane potential is maintained between -90 mV and +20 mV.


D.Ionic basis of ventricular action potential

Phase 0:The depolarization phase: Rapid activation (opening) of Na+ channels allows Na+ to rush into the cell. This causes fast depolarization of the cell to a level above 0 mV. The Na+ channels quickly inactivate, and Vm stops near +20 mV.

Tetrodotoxin (TTX; a toxin from puffer fish)--- blocks this Na channel.

Phase 1:The transient repolarization phase: Depolarization produced by Na+ influx leads to activation of a transient outward current mainly carried by K+. This current is called ITO. As the activation of ITO is transient, only a brief efflux of K+ occurs, causing a brief and limited repolarization. Because ITO is a repolarizing current, the magnitude of ITO regulates the duration of an action potential. A larger ITO results in shorter action potential duration.

4-aminopyridine - blocks ITO.


Phase 2:Plateau phase. Ca2+ influx occurs mainly during this phase. During this phase, inward Na+ and Ca2+ currents are balanced by an outward K+ current, which accounts for the relatively flat phase 2. Vm remains near 0 mV.

The magnitudes of currents are small and there is a fine balance between inward and outward currents to maintain a near zero net current. An increase in either inward or outward current at this time will tip the balance in favor of that current, and change the Vm. IK1 is decreased markedly during this phase due to depolarization (see the I-V relationship of IK1), and this is one important reason that the relatively long plateau phase exists.


Phase 3:Repolarization phase. The delayed rectifier K+ current starts to activate upon depolarization. As the delayed rectifier K+ current increases, the net balance is tipped in favor of the outward current, and repolarization begins. IK1 increases during repolarization during the last third of the repolarization phase and thus helps to restore the Vm to the resting potential faster.

Phase 4:The resting phase: During this period, IK1 is fully active and keeps the Vm near -90 mV as K+ is moving out of the cell. Recovery from inactivation occurs for Na+ and Ca2+ channels during this phase and gets ready to open when depolarization occurs.

Changes in the conductances of Na+, Ca2+ and K+ during various phases of the action potential of a ventricular cell (right)


Ca2+ current is activated upon depolarization. The activation and inactivation of Ca2+ current are slower than those of Na+ current. Majority of Ca2+ influx occurs during the plateau phase of the action potential and this Ca2+ influx is the trigger for further Ca2+ release from the sarcoplasmic reticulum and subsequent muscle contraction (Ca2+-induced Ca2+ release).

Depolarization from resting potential causes:
  1. Activation of Na current (INa; phase 0)
  2. Activation of transient outward K current (ITO)
  3. Activation of Ca current (ICa); slower onset
  4. Delayed activation of a K current (delayed rectifier K current; IK)
  5. Decrease in IK1

E.Ionic basis of the SA nodal (pacemaker) cell action potential.

Sinoatrial nodal cells are located near the junction between the superior vena cava and the right atrium. In sinoatrial node cells, only three phases are prominently observed.


Slow upstroke (depolarization) phase: Fast (TTX-sensitive) Na+ channels are in the inactivated state due to the level of the membrane potential which fluctuates between -60 and -40 mV. At these potentials, only the Ca2+ channels become activated upon depolarization. Since activation of Ca2+ current is slower than that of Na+ current, the upstroke of the action potential is also slower. In these cells, IK1 is absent, accounting for the partially depolarized (-60 to -40 mV) state of the SA nodal cells.


Repolarization phase.Delayed rectifier K+ current (IK) is responsible for the repolarization as in ventricular cells.


Pacemaker potential phase:

This is also called spontaneous diastolic depolarization phase. During this phase, slow spontaneous depolarization of membrane potential occurs. The gradual depolarization is due to two inward currents: First If and then ICa. A decrease in the delayed rectifier K+ repolarizing current during this phase is also important for the slow depolarization.

IF (“funny current”) is a Na+ current. It is different from the TTX-sensitive Na+ current that is responsible for the upstroke of the action potential (phase 0) in ventricular cells and non-pacemaker atrial cells.

There are two different types of Ca2+ channels that are involved in pacemaker action potential: T-Type and L-Type. T-Type mediates the part of the pacemaker potential whereas the L-Type produces the large depolarization. Initial depolarization is caused by IF that is activated by repolarization caused by IK. The membrane potential soon reaches the threshold for T-Type Ca2+ channels, causing Ca influx and further depolarization. The membrane potential then reaches the threshold for activation of L-Type Ca2+ channels, causing the upstroke of the action potential. (The Ca2+ current recorded in ventricular cells and non-pacemaker atrial cells is due to Ca2+ influx via the L-Type Ca2+ channels)

So if anyone asks which currents produce the pacemaker potential, your answer should be IF (increase), ICa (increase) and IK (decrease).

Increase in temperature (warming) increases the slope of the pacemaker potential. Cooling does the opposite (slower heart rate).



Acetylcholine decreases heart rate by activating muscarinic K+ current (IK.ACh) and by reducing If and ICa. Norepinephrine increases the heart rate by augmenting If and ICa.


Automaticity - ability to initiate a heart beat

Rhythmicity - frequency and regularity of pacemaking activity

Inotropy - related to changes in myocardial contractility

Chronotropy - heart rate

Ectopic pacemaker - cell or cells in regions of the heart other than SA node that can initiate pacemaking activity.


Overdrive suppression-Automaticity of pacemaking cells are suppressed temporarily after they are driven at high frequency. SA nodal cells fire at higher frequency than other latent pacemaker cells of the heart, and thus suppress the pacemaking activity of latent pacemakers which exist around the SA nodal cells. When true pacemaker cells become damaged and can not fire, other cells with the next highest rate of diastolic depolarization will begin to take over as the pacemaker of the heart. In Sick Sinus Syndrome, the SA nodal cells periodically cease firing. Since it takes several seconds for latent pacemakers to start to fire on their own, bradycardia (slowing of heart rate) results and blood supply to the body is reduced during this time.

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