potassium and calcium currents,with different sensitivities to blocking drugs,have been identified.Chloride currents (dotted arrows)produce both inward and outward membrane currents during the cardiac action potential. The Effect of Resting Potential on Action Potentials A key factor in the pathophysiology of arrhythmias and the actions of antiarrhythmic drugs is the relationship between the resting potential of a cell and the action potentials that can be evoked in it(Figure 4,left panel).Because the inactivation gates of sodium channels in the resting membrane close over the potential range-75 to-55 mV,fewer sodium channels are "available"for diffusion of sodium ions when an action potential is evoked from a resting potential of-60 mV than when it is evoked from a resting potential of-80 mV.Important consequences of the reduction in peak sodium permeability include reduced maximum upstroke velocity (for maximum rate of change of membrane voltage),reduced action potential amplitude,reduced excitability,and reduced conduction velocity. During the plateau of the action potential,most sodium channels are inactivated. Upon repolarization,recovery from inactivation takes place (in the terminology of Figure 2,the h gates reopen),making the channels again available for excitation.The time between phase 0 and sufficient recovery of sodium channels in phase 3 to permit a new propagated response to an external stimulus is the refractory period.Changes in refractoriness (determined by either altered recovery from inactivation or altered action potential duration)can be important in the genesis or suppression of certain arrhythmias.Another important effect of less negative resting potential is prolongation of this recovery time,as shown in Figure 4 (right panel).The prolongation of recovery time is reflected in an increase in the effective refractory period. A brief,sudden,depolarizing stimulus,whether caused by a propagating action potential or by an external electrode arrangement,causes the opening of large numbers of activation gates before a significant number of inactivation gates can close. In contrast,slow reduction (depolarization)of the resting potential,whether brought about by hyperkalemia,sodium pump blockade,or ischemic cell damage,results in depressed sodium currents during the upstrokes of action potentials.Depolarization of the resting potential to levels positive to -55 mV abolishes sodium currents,since all sodium channels are inactivated.However,such severely depolarized cells have been found to support special action potentials under circumstances that increase calcium permeability or decrease potassium permeability.These "slow responses"-slow upstroke velocity and slow conductiondepend on a calcium inward current and constitute the normal electrical activity in the sinoatrial and atrioventricular nodes, since these tissues have a normal resting potential in the range of-50 to-70 mV.Slow responses may also be important for certain arrhythmias.Modern techniques of molecular biology and electrophysiology can identify multiple subtypes of calcium 88 potassium and calcium currents, with different sensitivities to blocking drugs, have been identified. Chloride currents (dotted arrows) produce both inward and outward membrane currents during the cardiac action potential. The Effect of Resting Potential on Action Potentials A key factor in the pathophysiology of arrhythmias and the actions of antiarrhythmic drugs is the relationship between the resting potential of a cell and the action potentials that can be evoked in it (Figure 4, left panel). Because the inactivation gates of sodium channels in the resting membrane close over the potential range -75 to -55 mV, fewer sodium channels are "available" for diffusion of sodium ions when an action potential is evoked from a resting potential of -60 mV than when it is evoked from a resting potential of -80 mV. Important consequences of the reduction in peak sodium permeability include reduced maximum upstroke velocity (for maximum rate of change of membrane voltage), reduced action potential amplitude, reduced excitability, and reduced conduction velocity. During the plateau of the action potential, most sodium channels are inactivated. Upon repolarization, recovery from inactivation takes place (in the terminology of Figure 2, the h gates reopen), making the channels again available for excitation. The time between phase 0 and sufficient recovery of sodium channels in phase 3 to permit a new propagated response to an external stimulus is the refractory period. Changes in refractoriness (determined by either altered recovery from inactivation or altered action potential duration) can be important in the genesis or suppression of certain arrhythmias. Another important effect of less negative resting potential is prolongation of this recovery time, as shown in Figure 4 (right panel). The prolongation of recovery time is reflected in an increase in the effective refractory period. A brief, sudden, depolarizing stimulus, whether caused by a propagating action potential or by an external electrode arrangement, causes the opening of large numbers of activation gates before a significant number of inactivation gates can close. In contrast, slow reduction (depolarization) of the resting potential, whether brought about by hyperkalemia, sodium pump blockade, or ischemic cell damage, results in depressed sodium currents during the upstrokes of action potentials. Depolarization of the resting potential to levels positive to -55 mV abolishes sodium currents, since all sodium channels are inactivated. However, such severely depolarized cells have been found to support special action potentials under circumstances that increase calcium permeability or decrease potassium permeability. These "slow responses" - slow upstroke velocity and slow conductiondepend on a calcium inward current and constitute the normal electrical activity in the sinoatrial and atrioventricular nodes, since these tissues have a normal resting potential in the range of -50 to -70 mV. Slow responses may also be important for certain arrhythmias. Modern techniques of molecular biology and electrophysiology can identify multiple subtypes of calcium