and potassium channels.One way in which such subtypes may differ is in sensitivity to drug effects,so drugs targeting specific channel subtypes may be developed in the future. 里10,00 Drug 100 10.000 Control 1000 Drug 100 0 Contro -120-100-80 60 -120-100-80 60 Resting membrane potential(mV) Resting membrane potential(mV) Figure 4.Dependence of sodium channel function on the membrane potential preceding the stimulus.Left:The fraction of sodium channels available for opening in response to a stimulus is determined by the membrane potential immediately preceding the stimulus.The decrease in the fraction available when the resting potential is depolarized in the absence of a drug (control curve)results from the voltage-dependent closure of h gates in the channels.The curve labeled Drug illustrates the effect of a typical local anesthetic antiarrhythmic drug.Most sodium channels are inactivated during the plateau of the action potential.Right:The time constant for recovery from inactivation after repolarization also depends on the resting potential.In the absence of drug,recovery occurs in less than 10 ms at normal resting potentials (-85 to -95 mV).Depolarized cells recover more slowly (note logarithmic scale).In the presence of a sodium channel-blocking drug,the time constant of recovery is increased,but the increase is far greater at depolarized potentials than at more negative ones. MECHANISMS OF ARRHYTHMIAS Introduction Many factors can precipitate or exacerbate arrhythmias:ischemia,hypoxia,acidosis or alkalosis,electrolyte abnormalities,excessive catecholamine exposure,autonomic influences,drug toxicity (eg,digitalis or antiarrhythmic drugs),overstretching of cardiac fibers,and the presence of scarred or otherwise diseased tissue.However,all arrhythmias result from (1)disturbances in impulse formation,(2)disturbances in impulse conduction,or(3)both. 99 and potassium channels. One way in which such subtypes may differ is in sensitivity to drug effects, so drugs targeting specific channel subtypes may be developed in the future. Figure 4. Dependence of sodium channel function on the membrane potential preceding the stimulus. Left: The fraction of sodium channels available for opening in response to a stimulus is determined by the membrane potential immediately preceding the stimulus. The decrease in the fraction available when the resting potential is depolarized in the absence of a drug (control curve) results from the voltage-dependent closure of h gates in the channels. The curve labeled Drug illustrates the effect of a typical local anesthetic antiarrhythmic drug. Most sodium channels are inactivated during the plateau of the action potential. Right: The time constant for recovery from inactivation after repolarization also depends on the resting potential. In the absence of drug, recovery occurs in less than 10 ms at normal resting potentials (-85 to -95 mV). Depolarized cells recover more slowly (note logarithmic scale). In the presence of a sodium channel-blocking drug, the time constant of recovery is increased, but the increase is far greater at depolarized potentials than at more negative ones. MECHANISMS OF ARRHYTHMIAS Introduction Many factors can precipitate or exacerbate arrhythmias: ischemia, hypoxia, acidosis or alkalosis, electrolyte abnormalities, excessive catecholamine exposure, autonomic influences, drug toxicity (eg, digitalis or antiarrhythmic drugs), overstretching of cardiac fibers, and the presence of scarred or otherwise diseased tissue. However, all arrhythmias result from (1) disturbances in impulse formation, (2) disturbances in impulse conduction, or (3) both