Both membrane stretch and fatty acids directly activate large conductance Ca2+‐activated K+ channels in vascular smooth muscle cells

Abstract

Large conductance Ca 2+‐activated K+ channels in rabbit pulmonary artery smooth muscle cells are activated by membrane stretch and by arachidonic acid and other fatty acids. Activation by stretch appears to occur by a direct effect of stretch on the channel itself or a closely associated component. In excised inside‐out patches stretch activation was seen under conditions which precluded possible mechanisms involving cytosolic factors, release of Ca 2+ from intracellular stores, or stretch induced transmembrane flux of Ca 2+ or other ions potentially capable or activating the channel, Fatty acids also directly activate this channel. Like stretch activation, fatty acid activation occurs in excised inside‐out patches in the absence of cytosolic constituents. Moreover, the channel is activated by fatty acids which, unlike arachidonic acid, are not substrates for the cyclo‐oxygenase or lypoxygenase pathways, indicating that oxygenated metabolites do not mediate the response. Thus, four distinct types of stimuli (cytosolic Ca 2+, membrane potential, membrane stretch, and fatty acids) can directly affect the activity of this channel.