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

Abstract

Large conductance Ca"'-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"" from intracellular stores, or stretch induced transmombranc flux of Ca"" or other ions potentially capable of activatina the channel, Fatty acids al~o 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 subatrates for tile cyelo-oxygenase or lypoxygenasc pathways, indicating that oxygenated metabolltes do not mediate the response. Thus, four distinct types of stimuli (cytosolic Ca-". membrane potential, membrane stretch, and fatty acids) can directly affect the activity of this channel.

Modulation of calcium channel currents by arachidonic acid in single smooth muscle cells from vas deferens of the guinea‐pig

“…This type of direct action has also been suggested for the mechanism of the AA-induced increase in large conductance Ca-dependent K channel (BK channel) activity in pulmonary smooth muscle cells (Kirber et al, 1992). Since internal application of 0.3 mM GTPyS or 1 mM GDPfiS did not affect significantly the AA-induced decrease in IBa (Figure 6), activation of a GTP binding protein is unlikely to be involved in this AA effect, unlike the AA-induced regulation of the cardiac K+ channel (Kim et al, 1989;Scherer & Breitwieser, 1990).…”

“…Regulation of Ca2"-activated K+ channels in smooth muscle cells by AA, its metabolites or other fatty acids has been extensively studied (Bregestovski et al, 1988;Kirber et al, 1992;Gebremedhin et al, 1992;Hu & Kim, 1993). However, effects of AA on Ca2+ channel activity in smooth muscles has received less attention.…”

Some evidence against the involvement of arachidonic acid in muscarinic suppression of voltage‐gated calcium channel current in guinea‐pig ileal smooth muscle cells

“…The disappearance of the effect of AA in the virtual absence of cytosolic free Ca21 suggests that AA may increase the activity of the Ca2+-dependent potassium channels, as demonstrated in vascular smooth muscle cells (Kirber et al, 1992).…”

Human Podocytes Possess a Stretch-Sensitive, Ca2+-Activated K+ Channel

“…At the same time, intracellular Ca 2ϩ is raised, as a result both of Ca 2ϩ influx (19) and release from intracellular stores (20). This increase in Ca 2ϩ is accompanied by an increase in BK channel activity, which acts to moderate the degree of membrane depolarization (21); this is seen as a protective mechanism in limiting the degree of smooth muscle contraction such that the vessels remain patent. By analogy, one might hypothesize that the role of BK channels in podocytes is in the negative-feedback control of the membrane potential, thus moderating the degree of podocyte contraction in response to membrane stretch.…”