Role of calcium-activated potassium channels in the relaxation of tracheal smooth muscles by forskolin.
1. The role of calcium-activated potassium (KCa) channels in bronchodilation produced by a direct adenylyl cyclase activator, forskolin, was investigated. The involvement of intracellular cyclic AMP (cAMP) in the process was also examined. 2. The isometric tension records from guinea-pig tracheal smooth muscles indicated that application of charybdotoxin (ChTX), a selective inhibitor of large conductance KCa channels, led to a suppression of the relaxant effect of forskolin in the precontracted tissue by carbachol (CCh). However, the inhibitory action by ChTX had a much greater effect on the relaxation caused by isoproterenol than by forskolin. 3. In contrast to the effect of ChTX, glybenclamide, a cromakalim-sensitive K+ channel inhibitor and apamin, a small conductance KCa channel blocker, had no effects on the bronchodilation produced by forskolin. 4. The effects of forskolin and nifedipine on tone produced by high K+ was compared. Concentration-inhibition curves in guinea-pig trachealis precontracted by 20 mmol/L K+ solution were similar for forskolin and nifedipine. Conversely, relaxation by forskolin was significantly diminished when tissues were contracted with 40 mmol/L K+ solution, whereas nifedipine relaxations were unaffected. 5. A single channel record from a cell-attached patch in a porcine tracheal myocyte demonstrated that forskolin stimulates reversibly KCa channels without affecting the unitary amplitude. 6. The results are consistent with forskolin-induced relaxation occurring at least in part through the opening of ChTX-sensitive KCa channels, by means of a cAMP-dependent channel modulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Hiramatsu
T
T
Second Department of Internal Medicine, School of Medicine, Nagoya University, Japan.
Kume
H
H
Kotlikoff
M I
MI
Takagi
K
K
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D018999:Charybdotoxin; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D012604:Scorpion Venoms / Q000633:toxicity; D014132:Trachea / Q000187:drug effects
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D005576:Colforsin; D001030:Apamin; D002217:Carbachol; D000242:Cyclic AMP; D009543:Nifedipine; D005905:Glyburide; D002118:Calcium