title: The transduction system in the isoproterenol activation of the Ca(2+)-activated K+ channel in guinea pig taenia coli myocytes.
abstract: In freshly dispersed guinea pig taenia coli myocytes the activity of the large conductance Ca(2+)-activated K+ channel (maxi-K+ channel) predominates. The open probability (Po) of this channel is increased by micromolar concentrations of the beta-adrenergic agonist isoproterenol (ISO). Low concentrations of cholera toxin (CTX, 1 pM) and guanosine 5'-O-2-thiodiphosphate (GDP beta S, 0.5 mM) suppress the ISO-induced increase of Po. Higher concentrations of CTX (e.g., 0.5 nM) as well as forskolin and dibutyryl cAMP increase the Po. 1,9-Dideoxyforskolin, the forskolin analogue, which lacks the adenylate cyclase-stimulating effect, does not. A specific protein kinase A inhibitor (Wiptide), applied 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 mobilization, does not affect either the whole-cell outward K+ current during step depolarization or the Po. These observations show that ISO increases the Po of the maxi-K+ channels in the guinea pig taenia coli myocytes through the G protein-adenylate cyclase-protein kinase A system.
authors.affiliation: Department of Pharmacology, State University of New York, Downstate Medical Center, Brooklyn 11203.
authors.forename: S F
authors.initials: SF
authors.lastname: Fan
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: C Y
authors.initials: CY
authors.lastname: Kao
mesh_terms: D000262:Adenylyl Cyclases / Q000502:physiology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000502:physiology; D009132:Muscles / Q000166:cytology / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D019311:Staurosporine; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D005576:Colforsin; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D003994:Bucladesine; C023427:guanosine 5'-O-(2-thiodiphosphate); D002772:Cholera Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D019311:Staurosporine; D007545:Isoproterenol; D002118:Calcium