Characteristics of depressing effect of cycloprotobuxine-A on the maximal velocity of depolarization in myocardium.
The characteristics of the depressing effect of cycloprotobuxine-A on Vmax in isolated guinea pig myocardium were investigated with a standard microelectrode technique. Cycloprotobuxine-A 3-30 mumol/l produced a concentration-dependent decrease in Vmax, associated with a prolongation of the action potential duration. At 3 mumol/l, a small resting block of Vmax, but a pronounced use-dependent block was found. This use-dependent block increased progressively as stimulation frequency increased from 0.5 to 4.0 Hz. The time constant and rate for onset of use-dependent block were 2.0-7.3 s and 0.11-0.25 AP-1 (reciprocal action potential number), respectively. The time constant and half-life for recovery from use-dependent block were 11.8 and 8.1 s. Thus, the kinetics of the depressing effect of cycloprotobuxine-A on Vmax were intermediate. In muscles depolarized by high [K+]0, the resting block was enhanced slightly, while use-dependent block was greatly augmented. These results suggested that cycloprotobuxine-A could have a low affinity for resting Na+ channels but a much higher affinity for activated and/or inactivated Na+ channels, and that the use-, frequency- and voltage-dependent effects of cycloprotobuxine-A on Vmax may play an important role in preventing the development of cardiac arrhythmias.
Wang
Y X
YX
Department of Pharmacology, Fourth Military Medical University, Shaanxi, People's Republic of China.
Tan
Y H
YH
Sheng
B H
BH
Chen
S Y
SY
D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D007700:Kinetics; D015222:Sodium Channels / Q000187:drug effects
D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; C062783:cycloprotobuxine A