cAMP-dependent modulation of L-type calcium currents in mouse diaphragmatic cells.
The regulation of calcium channels by cAMP-dependent phosphorylation was investigated in the diaphragm muscle. Experiments were performed on dissociated costal diaphragmatic cells from 16- to 17-day-old fetal mice. The ionic current through calcium channels was measured using the whole cell clamp technique with barium as the charge carrier. A depolarizing pulse delivered from a holding potential of -80 mV elicited a low-threshold dihydropyridine (DHP)-insensitive T-type current and a high-threshold DHP-sensitive L-type current. Agents that either increase intracellular cAMP levels (forskolin, 10(-4) M, and dibutyryladenosine 3'-5' cyclic monophosphate, 10(-4) M) or inhibit cAMP degradation (theophylline, 10(-4) M) produced relative increases in L-type current amplitude of 24.4 +/- 13.8%, 13.4 +/- 4.6%, and 15.9 +/- 2.8% (p < 0.05), respectively. Current intensity increased after application of the beta-adrenergic agonist isoproterenol (10(-5) M, 16.5 +/- 3.6%, P < 0.005). None of these agents affected the T-type current. These results suggest that L-type calcium channel activities of the diaphragm muscle are regulated by cAMP-dependent phosphorylation.
Fratacci
M D
MD
INSERM, U296, Faculté de Médecine, Créteil, France.
Shimahara
T
T
Bournaud
R
R
Atlan
G
G
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003964:Diaphragm / Q000196:embryology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010766:Phosphorylation; D011247:Pregnancy; D013806:Theophylline / Q000494:pharmacology
D015220:Calcium Channels; D005576:Colforsin; D001464:Barium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D013806:Theophylline; D000242:Cyclic AMP; D009543:Nifedipine; D007545:Isoproterenol