Characteristics of depressing effect of cycloprotobuxine-A on the maximal velocity of depolarization in myocardium.

Abstract

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.

• Authors: Y X Wang, Y H Tan, B H Sheng, S Y Chen
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 222 Issue 2-3 Pg. 219-22 (Nov 10 1992) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1333406 (Publication Type: Journal Article)

Chemical References

• Alkaloids
• Anti-Arrhythmia Agents
• Sodium Channels
• cycloprotobuxine A

Topics

• Action Potentials (drug effects)
• Alkaloids (pharmacology)
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Electric Stimulation
• Guinea Pigs
• Heart (drug effects)
• Kinetics
• Sodium Channels (drug effects)