Effects of bencyclane on normal and cevadine-modified Na channels in frog skeletal muscle.
The effect of 10(-5) mol/l bencyclane on the repetitive electrical activity of muscle membrane was studied with the conventional microelectrode technique. Electrical activity was induced by repetitive stimulation in normal Ringer solution (train) or by a single depolarizing current pulse in the presence of 10(-6) mol/l cevadine (volley). Bencyclane decreased, in a use-dependent manner, the maximum rates of depolarization and repolarization (Vmax+ and Vmax-, resp.) of the action potentials both of the train and the volley. The inhibition of Vmax+ and Vmax- was proportional; however, it was stronger for the volleys than for the trains. The cycle length (mean interspike interval) of the volley was increased by bencyclane; the prolongation was progressive during consecutive cycles. The dissociation of bencyclane from the Na channel was studied by applying trains of different durations with equal pulse numbers. Bencyclane at a higher concentration (5 x 10(-5) mol/l) caused a reversible tonic block: the overshoot potentials, Vmax+ and Vmax- were markedly reduced. The reduction of Vmax- was slightly stronger than that of Vmax+. Slow membrane potential oscillation (SMPO) was evoked by treating the muscle with 10(-4) mol/l of cevadine. The administration of 5 x 10(-6) mol/l bencyclane decreased the frequency of SMPO, while 10(-5) mol/l bencyclane terminated the slow oscillation activity without changing its baseline potential. The present results indicate that bencyclane induces use-dependent inhibition of Na channels in muscle, similarly as do class 1 antiarrhytnmic drugs. Inhibition was observed with both normal and cevadine-modified Na channels.
Nánási
P P
PP
Department of Physiology, University Medical School of Debrecen, Hungary.
Bodnár
Z
Z
Dankó
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001537:Bencyclane / Q000494:pharmacology*; D003508:Cycloheptanes / Q000494:pharmacology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D011893:Rana esculenta; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D014702:Veratrine / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D003508:Cycloheptanes; D015222:Sodium Channels; D001537:Bencyclane; D014702:Veratrine