| Autor: |
Yamakage M; Department of Anesthesiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA., Hirshman CA, Croxton TL |
| Jazyk: |
angličtina |
| Zdroj: |
The American journal of physiology [Am J Physiol] 1996 Mar; Vol. 270 (3 Pt 1), pp. L338-45. |
| DOI: |
10.1152/ajplung.1996.270.3.L338 |
| Abstrakt: |
To directly investigate the possible role of large-conductance Ca2+ -activated K+ (KCa) channels in nitro-vasodilator-induced relaxation of airway smooth muscle, we used cell-attached patch-clamp techniques to test the effects of sodium nitroprusside (SNP) on KCa channels in freshly dispersed porcine tracheal smooth muscle cells. Channel open-state probability (nPo) increased approximately 13-fold with exposure to 10(-5) M SNP, and this was partially reversed by addition of the guanylate cyclase inhibitors methylene blue (3 X 10(-4) M) or LY-83583 (5 X 10(-5) M). Pretreatment with the guanosine 3',5' -cyclic monophosphate (cGMP)-dependent protein kinase (G kinase) inhibitor Rp-8-(p-chlorophenylthio) cGMP-phosphorothioate (2 X 10(-5) M) prevented activation of KCa channels by SNP. We also tested the ability of G kinase to directly activate KCa channels in inside-out patches. G kinase (2.5 U/microliter) with ATP (0.5 mM) and cGMP (0.1 mM), but not ATP and cGMP alone, increased nPo approximately 23-fold. We conclude that SNP activates KCa channels in airway smooth muscle via guanylate cyclase and G kinase. Phosphorylation of the channel protein by G kinase may account for this response. Consequent membrane hyperpolarization and inhibition of Ca2+ entry through voltage-dependent channels may contribute to SNP-induced relaxation of airway smooth muscle. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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