Effects of palmatine on potassium and calcium currents in isolated rat hepatocytes.
OBJECTIVE
To study the effects of palmatine, a known inhibitor on delayed rectifier potassium current and L-type calcium current (I(Ca,L)) in guinea pig ventricular myocytes, on the potassium and calcium currents in isolated rat hepatocytes.


METHODS
Tight-seal whole-cell patch-clamp techniques were performed to investigate the effects of palmatine on the delayed outward potassium currents (I(K)), inward rectifier potassium current (I(K1)) and Ca(2+) release-activated Ca(2+) current (I(CRAC)) in enzymatically isolated rat hepatocytes.


RESULTS
Palmatine 0.3-100 microM reduced I(K) in a concentration-dependent manner with EC(50) of 41.62+/-10.11 microM and n(H), 0.48+/-0.07 (n=8). The effect of the drug was poorly reversible after washout. When the bath solution was changed to tetraethylammonium (TEA) 8 mM, IK was inhibited. Palmatine 10 microM and 100 microM shifted the I-V curves of I(K) downward, and the block of I(K) was voltage-independent. Palmatine 0.3-100 microM also inhibited I(CRAC) in a concentration-dependent manner. The fitting parameters were as follows: EC(50)=51.19+/-15.18 microM, and n(H)=0.46+/-0.07 (n=8). The peak value of I(CRAC) in the I-V relationship was decreased by palmatine 10 microM and 100 microM. But the reverse potential of I(CRAC) occurred at Voltage=0 mV in all cells. Palmatine 0.3-100 microM failed to have any significant effect on either inward or outward components of I(K1) at any membrane potential examined.


CONCLUSIONS
The inhibitory effects on I(K) and I(CRAC) could be one of the mechanisms that palmatine exerts protective effect on hepatocytes.
Wang
Fang
F
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province China. wangfang0322@yahoo.com.cn
Zhou
Hong-Yi
HY
Cheng
Lan
L
Zhao
Gang
G
Zhou
Ji
J
Fu
Li-Ying
LY
Yao
Wei-Xing
WX
D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002469:Cell Separation; D004553:Electric Conductivity; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001600:Berberine Alkaloids; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C005413:palmatine; D002118:Calcium