Modulation of manganese currents by 1, 4-dihydropyridines, isoproterenol and forskolin in rabbit ventricular cells.
Although often used as a Ca(2+) channel blocker, Mn(2+), in fact, permeates through Ca(2+) channels. Under Na(+)-free conditions, depolarizing pulses evoked slowly-decaying Mn(2+) currents ( I(Mn)). Maximal I(Mn) densities in the presence of 5 and 20 mM Mn(2+) were 0.42+/-0.12 pA/pF (mean+/-SEM, n=17) and 1.23+/-0.10 pA/pF ( n=40), respectively. At 5 mM, the ratio of maximal amplitude of I(Mn) to that of the Ca(2+) current ( I(Ca)) was 0.079+/-0.009 ( n=8). I(Mn) elicited from a holding potential of -50 mV was depressed by nitrendipine (1 microM) by approximately 70%. Nitrendipine (0.3 microM) shifted the steady-state inactivation curve to more negative potentials and shifted the potential for half-maximal inactivation ( E(0.5)) from 1.3 to -8.8 mV and also decreased the time constant of decay of I(Mn) at 20 mV from 986.2 to 167.9 ms. BAY K 8644 (1 microM), isoproterenol (10 microM) and forskolin (10 microM) all increased I(Mn) and shifted the current/voltage ( I/ V) relationship to more negative potentials. The small, slowly-inactivating I(Mn) is thus modulated by dihydropyridine Ca(2+) channel modulators and cyclic AMP-mediated phosphorylation in a manner similar to other L-type Ca(2+) channel currents. L-type Ca(2+) channels are involved in the regulation of intracellular [Mn] in ventricular myocytes.
Masumiya
Haruko
H
Department of Physiology, Juntendo University School of Medicine, 113-8421, Tokyo, Japan.
Tsujikawa
Hiroto
H
Hino
Naoki
N
Ochi
Rikuo
R
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D008345:Manganese / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007473:Ion Channels; D005576:Colforsin; D008345:Manganese; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D009568:Nitrendipine; D000242:Cyclic AMP; D007545:Isoproterenol