Cannabinoids Inhibit L-type Calcium Current In Rat Cardiomyocytes

The purpose of this study was to examine the effects of anandamide on L-type calcium current (ICa-L) in cardiomyocytes of rats and the underlying mechanism. Anandamide (0.01～10μmol/L) decrease the voltage-dependently activated peak amplitude of ICa-L and upshift the current-voltage (I-V) curve. Anandamide (0.01～10mol/L) decrease the peak amplitude of ICa-L from 8.07±0.4pA/pF to 7.69±0.3pA/pF , 6.74±0.3pA/pF , 4.51±0.2pA/pF, 3.03±0.1pA/pF (p<0.05), respectively. The value of IC50 is 0.6381±0.1282μmol/L. Anandamide1μmol/L mmol/L shift the steady-state inactivation curve of ICa-L to the left and changed half inactivation potential(V1/2) from (-34.39±0.1873 ) mV to (-42.20±0.5996 ) mV, The value of k from 5.720±0.1504 to 6.358±0.4346 (P<0.05). Indicating that anandamide may modify the voltage-dependent inactivation of calcium channel . Anandamide did not affect the steady-state activation curve of ICa-L. AM281(10μmol/L) , a specific cannabinoid receptor (CB1) blocker , antagonized the effect of anandamide. While, AM630(10μmol/L), the specific cannabinoid receptor (CB2) blocker, did not had the effect .These effects suggest that Anandamide decrease ICa-L by shifting its inactivation curve to the left, such effect may be mediated by CB1.