Ca2+-activated K+channels in airway smooth muscle are inhibited by cytoplasmic adenosine triphosphate
✍ Scribed by Klaus Groschner; Shai D. Silberberg; Craig H. Gelband; Cornelis Breemen
- Publisher
- Springer
- Year
- 1991
- Tongue
- English
- Weight
- 613 KB
- Volume
- 417
- Category
- Article
- ISSN
- 0031-6768
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✦ Synopsis
Large-conductance Ca2+-activated K + channels were studied in membranes of cultured rabbit airway smooth muscle cells, using the patch-clamp technique. In cell-attached recordings, channel openings were rare and occurred only at very positive potentials. Bradykinin (10 gM), an agonist which releases Ca 2 § from the sarcoplasmic reticulum, transiently increased channel activity. The metabolic blocker 2,4-dinitrophenol (20 pM), which lowers cellular adenosine triphosphate (ATP) levels, induced a sustained increase of channel activity in cellattached patches. In excised patches, these channels had a slope conductance of 155 pS at 0 mV, were activated by depolarization and by increasing the Ca 2 § concentration at the cytoplasmic side above 10-7 tool/1. ATP, applied to the cytoplasmic side of the patches, dose-dependently decreased the channel's open-state probability. An inhibition constant (Ki) of 0.2 mmol/1 was found for the ATP-induced inhibition. ATP reduced the Ca 2 § sensitivity of the channel, shifting the Ca 2 + activation curve to the right and additionally reducing its steepness. Our results demonstrate that cytoplasmic ATP inhibits a large-conductance Ca 2 § K § channel in airway smooth muscle. This ATP modulation of Ca 2 § K + channels might serve as an important mechanism linking energy status and the contractile state of the cells.