Tetrandrine inhibits electrically induced [Ca2+]i transient in the isolated single rat cardiomyocyte.
The effect of tetrandrine on the electrically induced elevation of cytosolic Ca2+ concentration, [Ca2+]i, in the single isolated rat cardiomyocyte was studied with a fluorometric ratio method using fura-2 acetomethylester (fura-2/AM) was Ca2+ indicator. Tetrandrine (3-100 microM) concentration and time dependently inhibited the amplitude of the [Ca2+]i transient without any significant effect on the resting level of [Ca2+]i. At high concentrations (60-100 microM), tetrandrine also prolonged the time to reach the peak (t1.0) and the time to decline the 20% of the peak level (t0.2) of the electrically induced [Ca2+]i transient. The effect of tetrandrine was fast in onset and fully reversible upon washout. Tetrandrine (10 microM) partially inhibited the elevation of [Ca2+]i in response to KCl-induced depolarization. Verapamil and diltiazem mimicked the effects of tetrandrine given at low concentrations, but not at high concentrations. At high concentrations, tetrandrine reduced the magnitude of the caffeine-induced [Ca2+]i transient. Tetrandrine (100 microM) administered after thapsigargin, which itself decreased the amplitude and prolonged the duration of the electrically induced [Ca2+]i transient, further decreased the amplitude of the [Ca2+]i elevation. After ryanodine, which itself decreased the amplitude of the [Ca2+]i transient, 100 microM tetrandrine not only further reduced the amplitude, but also prolonged the duration of the electrically induced [Ca2+]i transient. These results provide evidence that in addition to its inhibitory effect on Ca2+ influx at the sarcolemma at the therapeutically relevant concentrations, tetrandrine at high concentrations may inhibit Ca2+ uptake into the sarcoplasmic reticulum.
Wang
H X
HX
Department of Physiology, Faculty of Medicine, University of Hong Kong, Pokfulum, Hong Kong.
Kwan
C Y
CY
Wong
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TM
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D012433:Ryanodine; C009438:tetrandrine; D002110:Caffeine; D011189:Potassium Chloride; D019284:Thapsigargin; D012964:Sodium; D014700:Verapamil; D004110:Diltiazem; D002118:Calcium