Independent modulation of L-type Ca2+ channel in guinea pig ventricular cells by nitrendipine and isoproterenol.
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.
Sonoda
S
S
Department of Anesthesiology, Nippon Medical School, Tokyo, Japan.
Ochi
R
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D005071:Evoked Potentials; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D009568:Nitrendipine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation
D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D005576:Colforsin; C038806:1,4-dihydropyridine; D009568:Nitrendipine; D007545:Isoproterenol