[Inhibitory action of CPU86035 on L-type calcium current in single ventricular myocyte of guinea pig].
OBJECTIVE
To investigate the effects of CPU86035, a recently synthesized tetrahydroberberine derivative, on the L-type calcium currents (I(Ca.L)) in single guinea pig ventricular myocytes.


METHODS
The effect of CPU86035 of different concentrations (50 approximately 250 micromomol/L) on I(Ca.L) in enzymatically dispersed single guinea pig ventricular myocytes was investigated by using whole-cell patch-clamp technique.


RESULTS
(1) CPU86035 concentration-dependently inhibited I(Ca.L), with the IC50 at 75 micromol/L. (2) The inhibition of CPU86035 on I(Ca.L) was dependent on the holding potential (HP). 75 micromol/L CPU86035 inhibited I(Ca.L) by 49% +/- 2% at HP = -40 mV, and 64% +/- 4% at HP = -80 mV. (3) The homeostatic activation curve of ICa.L shifted to the right toward more positive potentials in the presence of CPU86035, with a V(1/2) of 15.4 mV +/- 0.8 mV compared with that of 15.4 +/- 0.8 mV in the control. (4) The homeostatic inactivation curve of I(Ca.L) shifted to the right toward more positive potentials in the presence of CPU86035, with a V(1/2) of -12.6 mV +/- 2.7 mV compared with that of -19.1 mV +/- 2.5 mV in the control. (5) The recovery from inactivation became slower in the presence of CPU86035.


CONCLUSIONS
CPU86035 strongly inhibits the calcium channel, probably by binding to the channel in resting stage.
Li
Chun
C
People's Hospital of Peking University, Beijing 100044, China.
Guo
Jihong
J
Liu
Taifeng
T
D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques
C454066:CPU86035; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D001599:Berberine