Induction of calcium-dependent action potentials by 4-aminopyridine in potassium depolarized guinea-pig papillary muscle.

Exposure of guinea-pig papillary muscle to 22 mM K+ resulted in loss of electromechanical excitability accompanied by an elevation of mean electrical threshold by 8.96 V and a membrane depolarization of about 47.3 mV. After setting the threshold to a new sensitive level for stimulation, 4-AP (1.25-5 x 10(-3) M) could restore both the propagated action potentials typical for Ca2+ (e.g. resting potential: -46 mV; action potential amplitude: 74.25 mV; upstroke velocity: 11.4 V/sec; abolition by Ca(2+)-channel blokers) and contractions to papillary muscle cells, with further elevation of resting potential from -51.2 mV to -46 mV. Restoration of electromechanical activity by 4-AP was dose-dependent and susceptible to blockade with D600 (5 x 10(-7) M). From these data, it was concluded that 4-AP restored electrical and mechanical excitability by increasing membrane conductance to Ca2+ (gCa2+).