Dihydropyridine (DHP) Ca
2+ channel blockers decrease L-type Ca
2+ channel current (I
CaL) by enhancing steady-state inactivation, whereas
β-adrenergic stimulation increases I
CaL with small changes in the kinetics. We studied the effects of DHP Ca
2+ channel blockers on cardiac I
CaL augmented by
β-adrenergic stimulation. We recorded I
CaL as Ba
2+ currents (I
Ba) from guinea pig ventricular myocytes using the whole-cell patch clamp technique, and compared the effects of nitrendipine (NIT) in the absence and presence of isoproterenol (1 μM, ISO) or forskolin (10 μM, FSK). Maximal I
Ba elicited from a holding potential of -80 mV were diminished to 69.4±13.5% (mean and SE,
n=5) of control by NIT (100 nM) and the diminished I
Ba were increased to 180.3±23.2% of control by ISO in the presence of NIT, which was similar to the enhancement seen in the absence of NIT. NIT shifted the V
1/2 of the I
Ba inactivation curve from -34.6±1.9 mV (
n=5) to -48.7±1.2 mV, enhancing I
Ba decay with shortening T
1/2 at -10 mV from 164.6±24.2 ms (
n=7) to 105.4±15.2 ms. ISO elicited a small additional shift in the V
1/2 of I
Ba inactivation in the same direction. ISO and FSK each slowed I
Ba decay in the absence of NIT, but not in its presence. Thus,
β-adrenergic agonists increase and DHP Ca
2+ channel blockers decrease the amplitude of cardiac I
CaL independently and the kinetics of I
CaL is determined mainly by the latter when these drugs coexist.
View full abstract