Use-dependent effects of 4-aminopyridine on transient outward current in dog ventricular muscle

The use-dependent features of 4-aminopyridine-induced block of the transient outward current were investigated under voltage clamp conditions in dog ventricular myocardial bundles. The block depended strongly on the pattern of voltage clamp pulses. Its level (settled in rested membranes) became deeper at early time during depolarization. In contrast, prolonged depolarization (above 50 to 100 ms) produced relief of block. Our results suggest that the block strongly depends on the state of the channel gating system.