Activation block and trapping of penticainide, a disopyramide analogue, in the Na+ channel of rabbit cardiac Purkinje fibers.

The blocking mechanism of the Na+ channel by penticainide, a disopyramide analogue, was studied in rabbit cardiac Purkinje fibers. Na+ channel activity was measured directly by recording the slowly inactivating Na+ current or indirectly by measuring Vmax. The two-microelectrode technique was used to measure currents under voltage-clamp conditions or to impose different degrees and durations of depolarizing pulses. The experimental results show 1) that penticainide exerted a pronounced use-dependent block not dependent on the duration of the depolarizing pulse, 2) that no block was observed in the absence of stimulation, even when the membrane was depolarized by conditioning prepulses, and 3) that recovery was slower the more negative the holding potential but could be accelerated by repeating the depolarizing pulse; there was not only use-dependent block but also use-dependent unblock. It is concluded that penticainide binds to the open Na+ channel and is trapped when the activated channel returns to the rested state.