Use-dependent blockade of sodium channels induced by bencyclane in frog skeletal muscle and canine cardiac Purkinje fiber.
Applying conventional microelectrode technique, the effect of bencyclane was studied on the maximal rate of rise (Vmax) of the transmembrane action potential in frog skeletal muscle and canine cardiac Purkinje fiber. Bencyclane (10 microM) decreased the Vmax from 333.7 +/- 6.9 V/sec to 302.7 +/- 10.2 V/sec (n = 6, p less than 0.05) in skeletal muscle without changing the resting membrane potential. If repetitive stimulation with different constant cycle lengths was applied, a further, frequency-dependent decrease of Vmax developed in both tissues with similar frequency-dependence. In skeletal muscle bencyclane increased the time of 50% repolarization by 33.3 +/- 2.5% (n = 7, p less than 0.01) and decreased the overshoot potential by 11.3 +/- 0.72 mV (n = 7, p less than 0.01) measured at 250 msec cycle length. In cardiac Purkinje fiber bencyclane shortened the action potential duration (APD90) from 258.3 +/- 15.4 msec to 241.7 +/- 12.1 msec (n = 6, p less than 0.05) without changing the resting membrane potential and action potential amplitude measured at 500 msec cycle length. The comparable size of the Vmax-block at the same cycle lengths observed in skeletal muscle (short APD) and Purkinje fiber (long APD) suggests that the inhibition may by mainly attributed to the open sodium channel population. It was concluded that the antiarrhythmic action of bencyclane, based on the use-dependent blockade of sodium channels, might be an important component of the therapeutic effect of bencyclane.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001537:Bencyclane / Q000494:pharmacology*; D003508:Cycloheptanes / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009132:Muscles / Q000187:drug effects*; D011690:Purkinje Fibers / Q000187:drug effects*; D011893:Rana esculenta; D012964:Sodium / Q000378:metabolism*
D003508:Cycloheptanes; D007473:Ion Channels; D001537:Bencyclane; D012964:Sodium