THE TRANSDUCTION SYSTEM IN THE ISOPROTERENOL ACTIVATION OF THE CA2-ACTIVATED K+ CHANNEL IN GUINEA-PIG TAENIA-COLI MYOCYTES()

In freshly dispersed guinea pig taenia coli myocytes the activity of t he large conductance Ca2+-activated K+ channel (maxi-K+ channel) predo minates. The open probability (P(o)) of this channel is increased by m icromolar concentrations of the beta-adrenergic agonist isoproterenol (ISO). Low concentrations of cholera toxin (CTX, 1 pM) and guanosine 5 '-O-2-thiodiphosphate (GDPbetaS, 0.5 mM) suppress the ISO-induced incr ease of P(o). Higher concentrations of CTX (e.g., 0.5 nM) as well as f orskolin and dibutyryl cAMP increase the P(o). 1,9-Dideoxyforskolin, t he forskolin analogue, which lacks the adenylate cyclase-stimulating e ffect, does not. A specific protein kinase A inhibitor (Wiptide), appl ied intracellularly via diffusion from the patch electrode, suppresses the ISO-induced increase of whole-cell outward K+ current during step depolarization. In contrast, intracellularly applied protein kinase C (19-36), a specific protein kinase C inhibitor, has no effect on the whole-cell current. TMB-8, an inhibitor of intracellular calcium mobil ization, does not affect either the whole-cell outward K+ current duri ng step depolarization or the P(o). These observations show that ISO i ncreases the P(o) of the maxi-K+ channels in the guinea pig taenia col i myocytes through the G protein-adenylate cyclase-protein kinase A sy stem.