Publication Date:
2012-05-05
Description:
Major features of the transcellular signaling mechanism responsible for endothelium-dependent regulation of vascular smooth muscle tone are unresolved. We identified local calcium (Ca(2+)) signals ("sparklets") in the vascular endothelium of resistance arteries that represent Ca(2+) influx through single TRPV4 cation channels. Gating of individual TRPV4 channels within a four-channel cluster was cooperative, with activation of as few as three channels per cell causing maximal dilation through activation of endothelial cell intermediate (IK)- and small (SK)-conductance, Ca(2+)-sensitive potassium (K(+)) channels. Endothelial-dependent muscarinic receptor signaling also acted largely through TRPV4 sparklet-mediated stimulation of IK and SK channels to promote vasodilation. These results support the concept that Ca(2+) influx through single TRPV4 channels is leveraged by the amplifier effect of cooperative channel gating and the high Ca(2+) sensitivity of IK and SK channels to cause vasodilation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715993/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715993/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sonkusare, Swapnil K -- Bonev, Adrian D -- Ledoux, Jonathan -- Liedtke, Wolfgang -- Kotlikoff, Michael I -- Heppner, Thomas J -- Hill-Eubanks, David C -- Nelson, Mark T -- 1P01HL095488/HL/NHLBI NIH HHS/ -- 2-P20-RR-016435-06/RR/NCRR NIH HHS/ -- GM086736/GM/NIGMS NIH HHS/ -- HL044455/HL/NHLBI NIH HHS/ -- P01 HL095488/HL/NHLBI NIH HHS/ -- R01 HL098243/HL/NHLBI NIH HHS/ -- R01HL098243/HL/NHLBI NIH HHS/ -- R37 DK053832/DK/NIDDK NIH HHS/ -- R37DK053832/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2012 May 4;336(6081):597-601. doi: 10.1126/science.1216283.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, College of Medicine, University of Vermont, Burlington, VT 05405, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22556255" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium/*metabolism
;
*Calcium Signaling
;
Endothelial Cells/drug effects/*metabolism/physiology
;
Endothelium, Vascular/drug effects/metabolism/physiology
;
Intermediate-Conductance Calcium-Activated Potassium Channels/metabolism
;
Ion Channel Gating
;
Leucine/analogs & derivatives/pharmacology
;
Mesenteric Arteries/drug effects/*metabolism/physiology
;
Mice
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
Patch-Clamp Techniques
;
Receptors, Muscarinic/metabolism
;
Signal Transduction
;
Small-Conductance Calcium-Activated Potassium Channels/metabolism
;
Sulfonamides/pharmacology
;
TRPV Cation Channels/agonists/antagonists & inhibitors/*metabolism
;
*Vasodilation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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