Two distinct inactivation processes related to phosphorylation in cardiac L-type Ca(2+) channel currents.
We investigated the inactivation process of macroscopic cardiac L-type Ca(2+) channel currents using the whole cell patch-clamp technique with Na(+) as the current carrier. The inactivation process of the inward currents carried by Na(+) through the channel consisted of two components >0 mV. The time constant of the faster inactivating component (30.6 +/- 2.2 ms at 0 mV) decreased with depolarization, but the time constant of the slower inactivating component (489 +/- 21 ms at 0 mV) was not significantly influenced by the membrane potential. The inactivation process in the presence of isoproterenol (100 nM) consisted of a single component (538 +/- 60 ms at 0 mV). A protein kinase inhibitor, H-89, decreased the currents and attenuated the effects of isoproterenol. In the presence of cAMP (500 microM), the inactivation process consisted of a single slow component. We propose that the faster inactivating component represents a kinetic of the dephosphorylated or partially phosphorylated channel, and phosphorylation converts the kinetics into one with a different voltage dependency.
Mitarai
S
S
Department of Pharmacology, Nagasaki University, School of Medicine, Nagasaki 8528523, Japan.
Kaibara
M
M
Yano
K
K
Taniyama
K
K
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D012964:Sodium / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides
D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D015222:Sodium Channels; D013449:Sulfonamides; D012964:Sodium; D000242:Cyclic AMP; D007545:Isoproterenol; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide