Effects of phosphorylation-related drugs on slow Ca2+ tail current in guinea-pig detrusor cells

In isolated guinea-pig detrusor cells, large conditioning depolarizations e voke slowly deactivating Ca2+ tail currents, considered to represent the se cond open state. The possible involvement of channel phosphorylation in thi s open state was examined. Application of isoprenaline caused a marginal in crease in Ca2+ channel current evoked by simple depolarization, while forsk olin did not. During application of either drug, slow-tail currents were ne ver observed after simple depolarizations. The conditions necessary to indu ce 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-thiodip hosphate)) (in the pipette) or H-7 (1-(5-isoquinolinesulfonyl)-2-methylpipe razine dihydrochloride) (to the bathing solution) was applied. The frequent depolarization protocol, known to facilitate Ca2+ current via Ca2+ and cyc lic AMP-dependent phosphorylation mechanism(s) in cardiac myocytes, did not induce slow-tail currents. These results suggest that the transition of Ca 2+ channels to the second open state during large depolarization is not a r esult of (voltage-operated) channel phosphorylation itself. Possible underl ying mechanisms are discussed. (C) 1999 Elsevier Science B.V. All rights re served.