Comparison of effects of tetrandrine on ionic channels of isolated rat neurohypophysial terminals and Y1 mouse adrenocortical tumor cells.
The effects of tetrandrine on the voltage-gated Ca2+, K+, and Na+ channels of the isolated rat neurohypophysial nerve terminals and Y1 mouse adrenocortical tumor cells were studied using standard and perforated patch-clamp techniques. Among the inward ionic currents, the T-type Ca2+ channel current (I(Ca)) in the Y1 cell line was strongly inhibited (by 52.9%) by a low concentration (13 mumol.L-1) of externally applied tetrandrine. The L-type I(Ca) in the isolated nerve terminals was also strongly inhibited (by 54.2%) by externally applied tetrandrine 33 mumol.L-1, whereas the N-type I(Ca) and Na+ current were not significantly affected by the same dose of the alkaloid. While it had no effect on the fast, transient K+ channels, external application of tetrandrine 1 mumol.L-1 blocked a slowly-gating, maxi Ca(2+)-activated K+ (K+(Ca)) channel in the nerve terminals, decreasing its P(o) by 84.4%.


CONCLUSIONS
(1) The order of the sensitivities of ionic channels to tetrandrine is K+(Ca) > T- > L- > N-type Ca2+ > Na+; (2) tetrandrine serves as a specific blocker of the slowly-gating K+(Ca) channel.
Wang
G
G
Worcester Foundation for Experimental Biology, Shrewsbury, MA 01545.
Jiang
M X
MX
Coyne
M D
MD
Lemos
J R
JR
D000236:Adenoma / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000473:pathology*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D051379:Mice; D009411:Nerve Endings / Q000187:drug effects; D010904:Pituitary Gland, Posterior / Q000187:drug effects*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D007473:Ion Channels; C009438:tetrandrine