1995 Fiscal Year Final Research Report Summary
Role of Ca-activated K channel and Na pump in the regulation of airway smmoth muscle tone.
| Project/Area Number |
06670632
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tokyo Women's Medical College |
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Principal Investigator |
TAMAOKI Jun Tokyo Women's Medical College, First Department of Medicine, Assistant Professor, 医学部, 講師 (60147395)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Airway smooth muscle / Ion channel / Patch clamp / cyclic nucleotide / asthma / Bronchodilator |
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| Research Abstract |
1. Muscle contractile and relaxant responses
Isolated bronchial segments were mounted in organ chambers and the contractile responses to acetylcholine and the relaxant responses to various bronchodilating agents were determined in the presence and absence of K channel blockers and ouabain. Acetylcholine-induced contrction was potentiated by charybdotoxin and ouabain, and the relaxant responses to salbutamol, forskolin and nitroprusside were attenuated by these drugs, whereas glibenclamide and apamin had no effect. Thus, Ca-activated K channel and Na pump play roles in the regulation of airway smooth muscle tone by depolarizing membrane potential.
2. Accumulation of cyclic nucleotides
Intracellular cyclic nucleotide concentrations were determined in the presence and absence of charybdotoxin and ouabain. Salbutamol and forskolin increased cAMP conctents and nitroprusside increased cGMP contents, and these effects were not altered by charybdotoxin and ouabain, indicating that intracellular cAMP and cGMP directly stimulate Ca-activated K channel and Na pump in airway smooth muscle cells.
3. Patch clamp studies
Addition of DBcAMP and DBcGMP each caused single K channel ion current. Therefore, it was confirmed that these cyclic nucleotides produce Ca-activated K channel opening and Na-K-ATPase activation.
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