Key result
Nitrendipine decreased maximal L-type Ca2+ channel current to 69.4% of control and accelerated its decay, while isoproterenol increased the diminished current to 180.3% without reversing the accelerated decay.
Absolute Event Rate: 69.4% vs 100%
p-value: p=<0.05
Beta-adrenergic agonists and dihydropyridine calcium channel blockers independently modulate the amplitude of cardiac L-type calcium currents, with the blocker primarily determining the inactivation kinetics when both are present.
Does not support changes in nitrendipine or isoproterenol use; leaves open whether independent amplitude and kinetic effects translate to human myocardium.
Dihydropyridine (DHP) Ca2+ channel blockers decrease L-type Ca2+ channel current (I(CaL)) by enhancing steady-state inactivation, whereas beta-adrenergic stimulation increases I(CaL) with small changes in the kinetics. We studied the effects of DHP Ca2+ channel blockers on cardiac I(CaL) augmented by beta-adrenergic stimulation. We recorded I(CaL) as Ba2+ 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 microM, ISO) or forskolin (10 microM, 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, beta-adrenergic agonists increase and DHP Ca2+ 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.
No takes yet. Share an insight, caveat, or question.
Sonoda et al. (2001) studied L-type Ca2+ channel modulation. Nitrendipine and Isoproterenol vs. Control (absence of drugs) was evaluated on Maximal IBa (barium current) amplitude (p=<0.05). Nitrendipine decreased maximal L-type Ca2+ channel current to 69.4% of control and accelerated its decay, while isoproterenol increased the diminished current to 180.3% without reversing the accelerated decay.