title: cAMP and forskolin inhibit potassium currents in rat taste receptor cells by different mechanisms.
abstract: In gustatory transduction, adenosine 3',5'-cyclic monophosphate (cAMP) has been suggested to close potassium channels when elevated by sweet stimuli or to open cAMP-gated cation channels when depressed by bitter stimuli. These experiments examine the effect of cAMP on whole cell currents from posterior taste receptor cells with standard patch-clamp techniques. Elevating cytosolic cAMP by pipette administration, membrane-permeant analogs [8-(4-chlorophenylthio)-cAMP (CPT-cAMP) and dibutyryl-cAMP], or by phosphodiesterase inhibition [3-isobutyl-1-methylxanthine (IBMX)] produced poorly reversible inhibitions of outward potassium currents by up to 33%. Unexpectedly, middle to high concentrations of forskolin (> 5 microM) profoundly and reversibly inhibited these currents (95%) with greatly accelerated inactivation kinetics. 1,9-Dideoxyforskolin, an ineffective activator of adenylate cyclase, was similarly potent. Kinase inhibitors effectively blocked the effects of cAMP elevations produced by IBMX or CPT-cAMP but did not block these forskolin actions. However, at low concentrations (5 microM), forskolin reduced potassium currents in a phosphorylation-dependent manner. Collectively, these data suggest that cAMP produces a phosphorylation-dependent inhibition of outward potassium currents but that forskolin's actions are independent of cAMP or phosphorylation except at low concentration. cAMP was also effective in altering the waveform of the gustatory action potential, implying it may modify transmission of gustatory information to the brain.
authors.affiliation: Indiana University School of Medicine, Center for Medical Education, Ball State University, Muncie 47306, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Herness
authors.forename: X D
authors.initials: XD
authors.lastname: Sun
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013650:Taste Buds / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013873:Thionucleotides; D005576:Colforsin; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D003994:Bucladesine; D000242:Cyclic AMP; C047983:1,9-dideoxyforskolin; D015056:1-Methyl-3-isobutylxanthine