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. CONCLUSION: CPU86035 strongly inhibits the calcium channel, probably by binding to the channel in resting stage.
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. CONCLUSION:CPU86035 strongly inhibits the calcium channel, probably by binding to the channel in resting stage.