Effects of tetrandrine on Ca(2+)- and Na(+)-currents of single bullfrog cardiomyocytes.
Tetrandrine is a natural alkaloid classified as a calcium antagonist. However, its precise actions on Ca(2+)-currents in cardiac cells have not been fully characterized. In the present study, we have investigated the mechanism of action of tetrandrine on the Ca(2+)-currents of single bullfrog cardiac cells, using the patch-clamp technique. Tetrandrine slightly increased ICaL from negative holding potentials (-100 mV) at low concentrations (10 nM-1 microM) and inhibited it at higher concentrations. At depolarized holding potentials (-50 mV) only an enhanced inhibition was seen. Tetrandrine blockade of the L-type Ca(2+)-current (ICaL) was mostly tonic. This is similar to ICaL blockade by nifedipine but not by verapamil, the latter being mostly use-dependent. Use-dependent effects of tetrandrine and nifedipine were evident at high rates. Availability curves were shifted leftwards (10-12 mV) by tetrandrine (10 microM) and nifedipine (1 microM). The T-type Ca(2+)-current (ICaT), although less sensitive, was decreased by both agents in a voltage-independent way. Tetrandrine (10-30 microM) but not nifedipine (1-10 microM), depressed the Na(+)-current (INa) in tonic, use- and voltage-dependent manners. We conclude that tetrandrine and nifedipine share some common actions on cardiac Ca(2+)-channels, while showing differences in their actions on Na(+)-channels. The depression of INa by tetrandrine suggests it could be effective on supraventricular tachycardias.
Rubio
L S
LS
Laboratorio de Electrofisiologia, Instituto de Cardiologia y Cirugia Cardiovascular, La Habana, Cuba.
Garrido
G
G
Llanes
L
L
Alvarez
J L
JL
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology* / Q000648:ultrastructure; D009543:Nifedipine / Q000494:pharmacology; D011892:Rana catesbeiana / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D000470:Alkaloids; D044182:Benzylisoquinolines; D015220:Calcium Channels; D015222:Sodium Channels; C009438:tetrandrine; D014700:Verapamil; D009543:Nifedipine