Effects of phosphorylation-related drugs on slow Ca2+ tail current in guinea-pig detrusor cells.
In isolated guinea-pig detrusor cells, large conditioning depolarizations evoke slowly deactivating Ca2+ tail currents, considered to represent the second open state. The possible involvement of channel phosphorylation in this open state was examined. Application of isoprenaline caused a marginal increase in Ca2+ channel current evoked by simple depolarization, while forskolin did not. During application of either drug, slow-tail currents were never observed after simple depolarizations. The conditions necessary to induce slow-tail currents were not changed, even when cyclic AMP, ATP-gamma-S (adenosine 5'-O-(3-thiotriphosphate)), GDP-beta-S (guanosine 5'-O-(2-thiodiphosphate)) (in the pipette) or H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride) (to the bathing solution) was applied. The frequent depolarization protocol, known to facilitate Ca2+ current via Ca2+ and cyclic AMP-dependent phosphorylation mechanism(s) in cardiac myocytes, did not induce slow-tail currents. These results suggest that the transition of Ca2+ channels to the second open state during large depolarization is not a result of (voltage-operated) channel phosphorylation itself. Possible underlying mechanisms are discussed.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D001743:Urinary Bladder / Q000187:drug effects