Redox modulation of basal and β-adrenergically stimulated cardiac L-type Ca2+ channel activity by phenylarsine oxide

摘要: 1. Phenylarsine oxide (PAO) is commonly used to inhibit tyrosine phosphatase activity. However, PAO can affect a variety of different processes because its ability promote sulfhydryl oxidation. In the present study, we investigated effects that has on basal and beta-adrenergically stimulated L-type Ca(2+) channel activity in isolated cardiac myocytes. 2. Extracellular application transiently activity, whereas it irreversibly inhibited protein kinase A (PKA)-dependent regulation by isoproterenol, forskolin 8-CPT-cAMP (8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate). also presence adenosine 5'-(3-thiotriphosphate) tetralithium salt. 3. Neither stimulatory nor inhibitory were affected inhibitor lavendustin A, suggesting phosphorylation not involved. 4. sulfhydryl-reducing agent dithiothreitol (DTT) antagonized both PAO. Yet, following intracellular dialysis with DTT, only effect was antagonized. 5. The mimicked intracellular, but extracellular membrane impermeant thiol oxidant 5,5'-dithio-bis(2-nitrobenzoic acid). 6. These results suggest from oxidation residues at an site due redox affects response PKA-dependent phosphorylation. It concluded state cell may play critical role modulating beta-adrenergic responsiveness