Voltage- and use-dependent effect of 7-chlor-benzyltetrahydropalmatine on sodium currents in guinea pig ventricular myocytes.
The whole-cell patch-clamp technique was employed to obtain information about the voltage-dependence and kinetics of interaction of 7-chlor-benzyltetrahydropalmatine (7-Cl-BTHP) with cardiac sodium channels. 7-Cl-BTHP (30 mol/L) significantly decreased the peak sodium current (from 7.8 +/- 1.8 nA to 5.3 +/- 1.4 nA, P < 0.01, n = 5), without producing a shift of the current-voltage curve. It shifted the inactivation curves of sodium current to hyperpolarized potentials, and the V0.5 was shifted from -(82.5 +/- 2.5) mV to -(95 +/- 2.4) mV (P < 0.05, n = 4). 7-Cl-BTHP produced a significant use-dependent effect that was proportional to the duration of the voltage step. In addition, 7-Cl-BTHP slowed the recovery of sodium channel from inactivation, which could explain its use-dependent effects on sodium current. The characteristics of 7-Cl-BTHP blockage suggest that this agent binds preferentially to inactivated sodium channels.
Yan
S
S
Department of Pharmacology, Tongji Medical University, Wuhan.
Li
X
X
Yao
W
W
Xia
G
G
Jigang
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D001600:Berberine Alkaloids; D015222:Sodium Channels; C005413:palmatine