Abstract
The effects of the K-blocking agent 4-aminopyridine (4-AP) on the action potential and membrane currents of the sheep cardiac Purkinje fiber were studied. 4-AP slowed the rate of phase 1 repolarization and shifted the plateau of the action potential to less negative potentials. In 4-AP, the substitution of Na methylsulfate or methanesulfonate for the NaCl or Tyrode''s solution further slowed the rate of phase 1 repolarization, even though Cl replacement has no effect on the untreated preparation. In voltage clamp experiments. 4-AP rapidly and reversibly reduced the early peak of outward current that occurs when the Purkinje fiber membrane is voltage-clamped to potentials positive to -20 mV. In addition, 4-AP reduced the steady outward current at the end of clamp steps positive to -40 mV. 4-AP did not change the slow inward current over the range of -60 to -40 mV, nor did it greatly change the current tails that were used as a measure of slow inward conductance at more positive potentials. 4-AP did not block the inward rectifying K currents, IK1 and IK2. A phasic outward current component that was insensitive to 4-AP was reduced by Cl replacement. The early outward current has 2 components: a Cl-sensitive component plus a 4-AP-sensitive component. Since a portion of the steady-state current was sensitive to 4-AP, the early outward current does not fully inactivate or 4-AP blocks a component of time-independent background current.