Effects of calcium channel blockers on calcium release-activated calcium currents in rat hepatocytes.
OBJECTIVE
To study the influences of calcium channel blockers on calcium release-activated calcium currents (ICRAC) in rat hepatocytes.


METHODS
Whole-cell patch-clamp technique was used.


RESULTS
The peak amplitude of ICRAC was -0.41 nA +/- 0.09 nA (n = 15), its reversal potential was about 0 mV. Verapamil (Ver), diltiazem (Dil), and nifedipine (Nif) decreased ICRAC strikingly, without affecting its reversal potential. The inhibitory rate of Ver 5 mumol.L-1 was 40% +/- 12% (n = 3), Ver 50 mumol.L-1 reduced the peak amplitude of ICRAC from -0.49 nA +/- 0.12 nA to -0.20 nA +/- 0.09 nA (P < 0.01 vs control, n = 5). The inhibitory rate was 57% +/- 15%. Dil 50 mumol.L-1 and Nif reduced ICRAC from -0.43 nA +/- 0.10 nA to -0.29 nA +/- 0.07 nA (P < 0.01 vs control, n = 5), from -0.32 nA +/- 0.08 nA to -0.27 nA +/- 0.08 nA (P < 0.01 vs control, n = 5). The inhibitory rate was 31% +/- 11%, 19% +/- 7%, respectively. The amplitude of ICRAC was dependent on extracellular Ca2+ concentration. The peak amplitude of ICRAC was -0.21 nA +/- 0.08 nA (n = 3) in Tyrode's solution with Ca2+ 1.8 mmol.L-1 (P < 0.01 vs the peak amplitude of ICRAC in external solution with Ca2+ 10 mmol.L-1).


CONCLUSIONS
The three calcium antagonists inhibited ICRAC effectively and protected hepatocytes from calcium overload via the inhibition of ICRAC.
Cui
G Y
GY
Department of Pharmacology, China Medical University, Shenyang, China.
Li
J M
JM
Cui
H
H
Hao
L Y
LY
Liu
D J
DJ
Zhang
K Y
KY
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000166:cytology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine