scholarly journals Protein kinase C modulates basal myogenic tone in resistance arteries from the cerebral circulation.

1991 ◽  
Vol 68 (2) ◽  
pp. 359-367 ◽  
Author(s):  
G Osol ◽  
I Laher ◽  
M Cipolla
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cerebral Circulation ◽  
Myogenic Tone ◽  
Resistance Arteries ◽  
Kinase C

Diacylglycerol and protein kinase C activate cation channels involved in myogenic tone

2002 ◽  
Vol 283 (6) ◽  
pp. H2196-H2201 ◽  
Author(s):  
Donald F. Slish ◽  
Donald G. Welsh ◽  
Joseph E. Brayden
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Transient Receptor Potential Channels ◽  
Cell Swelling ◽  
Cation Channels ◽  
Myogenic Tone ◽  
Resistance Arteries ◽  
Kinase C ◽  
Intravascular Pressure

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.

scholarly journals Protein Kinase C θ Activation Induces Insulin-Mediated Constriction of Muscle Resistance Arteries

Diabetes ◽  
2007 ◽  
Vol 57 (3) ◽  
pp. 706-713 ◽  
Author(s):  
Wineke Bakker ◽  
Pieter Sipkema ◽  
Coen D.A. Stehouwer ◽  
Erik H. Serne ◽  
Yvo M. Smulders ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Resistance Arteries ◽  
Kinase C

Protein kinase C regulates vascular myogenic tone through activation of TRPM4

2007 ◽  
Vol 292 (6) ◽  
pp. H2613-H2622 ◽  
Author(s):  
Scott Earley ◽  
Stephen V. Straub ◽  
Joseph E. Brayden
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Antisense Oligonucleotides ◽  
Cerebral Arteries ◽  
Myogenic Tone ◽  
Kinase C ◽  
Intracellular Ca ◽  
Cell Depolarization ◽  
Stimulation Of

Myogenic vasoconstriction results from pressure-induced vascular smooth muscle cell depolarization and Ca2+ influx via voltage-dependent Ca2+ channels, a process that is significantly attenuated by inhibition of protein kinase C (PKC). It was recently reported that the melastatin transient receptor potential (TRP) channel TRPM4 is a critical mediator of pressure-induced smooth muscle depolarization and constriction in cerebral arteries. Interestingly, PKC activity enhances the activation of cloned TRPM4 channels expressed in cultured cells by increasing sensitivity of the channel to intracellular Ca2+. Thus we postulated that PKC-dependent activation of TRPM4 might be a critical mediator of vascular myogenic tone. We report here that PKC inhibition attenuated pressure-induced constriction of cerebral vessels and that stimulation of PKC activity with phorbol 12-myristate 13-acetate (PMA) enhanced the development of myogenic tone. In freshly isolated cerebral artery myocytes, we identified a Ca2+-dependent, rapidly inactivating, outwardly rectifying, iberiotoxin-insensitive cation current with properties similar to those of expressed TRPM4 channels. Stimulation of PKC activity with PMA increased the intracellular Ca2+ sensitivity of this current in vascular smooth muscle cells. To validate TRPM4 as a target of PKC regulation, antisense technology was used to suppress TRPM4 expression in isolated cerebral arteries. Under these conditions, the magnitude of TRPM4-like currents was diminished in cells from arteries treated with antisense oligonucleotides compared with controls, identifying TRPM4 as the molecular entity responsible for the PKC-activated current. Furthermore, the extent of PKC-induced smooth muscle cell depolarization and vasoconstriction was significantly decreased in arteries treated with TRPM4 antisense oligonucleotides compared with controls. We conclude that PKC-dependent regulation of TRPM4 activity contributes to the control of cerebral artery myogenic tone.

Effects of staurosporine and calphostin C, two structurally unrelated inhibitors of protein kinase C, on vascular tone

1993 ◽  
Vol 71 (7) ◽  
pp. 521-524 ◽  
Author(s):  
Daniel Henrion ◽  
Ismail Laher
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Blood Vessels ◽  
Myosin Light Chain ◽  
Facial Artery ◽  
Myogenic Tone ◽  
Calphostin C ◽  
Kinase C ◽  
Biochemical Studies ◽  
Facial Vein

In isolated rings of the rabbit facial vein, facial artery, and aorta, calphostin C and staurosporine, inhibitors of protein kinase C, reduced myogenic tone and norepinephrine (1 μM), K+ (80 mM), and Ca2+ (1.6 mM) induced tone. In all instances, staurosporine was more potent than calphostin C. In contrast to staurosporine, the IC50 value of calphostin C against myogenic tone was similar to that recorded for protein kinase C in biochemical studies (0.086 vs. 0.050 μM) and the average IC50 values of calphostin C against norepinephrine (2.2 μM), K+ (3.3 μM), and Ca2+ (4.3 μM) in the three vessels were similar to that for myosin light-chain kinase in biochemical studies (>5.0 μM). In the facial vein, calphostin C was 59-foid more potent against myogenic tone than against Ca2+-induced tone and 8-fold more specific for myogenic tone than was staurosporine. In addition, at concentrations not affecting K+ (80 mM) induced tone, calphostin C suppressed 1-oleoyl-2-acetyl-sn-glycerol induced tone in the facial vein, whereas staurosporine only attenuated it by 65%. Thus calphostin C inhibits protein kinase C dependent tone in isolated blood vessels to a greater extent than does staurosporine.Key words: staurosporine, calphostin C, myogenic tone, protein kinase C, blood vessels.

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