ISSN:
1432-2013
Keywords:
Airway smooth muscle
;
Patch-clamp
;
Ca2+-activated K+ channels
;
ATP sensitivity
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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 μM), an agonist which releases Ca2+ from the sarcoplasmic reticulum, transiently increased channel activity. The metabolic blocker 2,4-dinitrophenol (20 μM), which lowers cellular adenosine triphosphate (ATP) levels, induced a sustained increase of channel activity in cell-attached patches. In excised patches, these channels had a slope conductance of 155 pS at 0 mV, were activated by depolarization and by increasing the Ca2+ concentration at the cytoplasmic side above 10−7 mol/l. ATP, applied to the cytoplasmic side of the patches, dose-dependently decreased the channel's open-state probability. An inhibition constant (K i) of 0.2 mmol/l was found for the ATP-induced inhibition. ATP reduced the Ca2+ sensitivity of the channel, shifting the Ca2+ activation curve to the right and additionally reducing its steepness. Our results demonstrate that cytoplasmic ATP inhibits a large-conductance Ca2+-activated K+ channel in airway smooth muscle. This ATP modulation of Ca2+-activated K+ channels might serve as an important mechanism linking energy status and the contractile state of the cells.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00370948
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