Diacylglycerol and protein kinase C activate cation channels involved in myogenic tone.
The smooth muscle cells of resistance arteries depolarize and contract when intravascular pressure is elevated. This is a central characteristic of myogenic tone, which plays an important role in regulation of blood flow in many vascular beds. Pressure-induced vascular smooth muscle depolarization depends in part on the activation of cation channels. Here, we show that activation of these smooth muscle cation channels and pressure-induced depolarization are mediated by protein kinase C in cerebral resistance arteries. Diacylglycerol, phorbol myristate acetate, and cell swelling activate a cation current that we have previously shown is mediated by transient receptor potential channels. These currents, as well as the smooth muscle cell depolarizations of intact arteries induced by diacylglycerol, phorbol ester, and elevation of intravascular pressure, are nearly eliminated by protein kinase C inhibitors. These results suggest a major mechanism of myogenic tone involves mechanotransduction through phospholipase C, diacylglycerol production, and protein kinase C activation, which increase cation channel activity. The associated depolarization activates L-type calcium channels, leading to increased intracellular calcium and vasoconstriction.
Slish
Donald F
DF
Department of Biological Science, Plattsburgh State University, New York 12901, USA.
Welsh
Donald G
DG
Brayden
Joseph E
JE
D000217:Acyltransferases / Q000494:pharmacology*; D000818:Animals; D027682:Cation Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D002469:Cell Separation; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D051048:Diacylglycerol O-Acyltransferase; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009129:Muscle Tonus / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D027682:Cation Transport Proteins; D002412:Cations; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase; D011494:Protein Kinases; D011493:Protein Kinase C