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What did the smooth muscle cell say to the endothelial cell?
Abstract   Peer reviewed

What did the smooth muscle cell say to the endothelial cell?

F Plane, R Tam, Shaun L Sandow and P Kerr
Canadian Journal of Physiology and Pharmacology, Vol.90, p.674
Anniversary Symposium of the Department of Pharmacology at the University of Alberta, 50th (Edmonton, Canada, 05-Aug-2011–06-Aug-2011)
2012
DOI: https://doi.org/10.1139/y11-104
url
https://doi.org/10.1139/y11-104View
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Abstract

Pharmacology and Pharmaceutical Sciences Medical Physiology endothelium smooth muscle
The endothelium, the single layer of cells lining all blood vessels,is a key regulator of blood flow and blood pressure within the body. Endothelial cells influence the contractile state of the surrounding smooth muscle cells via release of diffusible factors, such as nitric oxide (NO), and by direct electrical coupling via myoendothelial gap junctions (MEGJs). The majority of studies in this area have focused on chemical and physical stimuli that act directly on endothelial cells. It has long been held that arterial vasoconstriction is limited by the endothelium, but how contraction of smooth muscle cells leads to activation of the endothelium has not been addressed. We propose that inositol 1,4,5 trisphosphate (IP3) generated by vasoconstrictors crosses MEGJs, elicits Ca2+ release from IP3 receptors and activates intermediate conductance Ca2+-activated K+ (IKCa) channels to elicit a negative feedback response. Constriction and depolarization of rat mesenteric arteries to phenylephrine was enhanced by endothelial removal. Selective application of xestaspongin, an IP3 receptor inhibitor, to the lumen of pressurized rat mesenteric resistance arteries, or superfusion of the vessels with an inhibitor of IKCa channels, enhanced vasoconstriction to phenylephrine. Application of phenylephrine depolarized the smooth muscle membrane potential, but caused a small, significant hyperpolarization of endothelial cell membrane potential. In the presence of IKCa channel block, this hyperpolarization was lost and significant endothelial depolarization to phenylephrine was observed. Ca2+ imaging showed that stimulation of smooth muscle cells by phenylephrine is associated with discrete, localized increases in Ca2+ within endothelial cells. Ultrastructural studies revealed IP3 receptors and IKCa channels localized at MEGJs in mesenteric arteries. These data indicate that IP3R and IKCa channels are central to endothelium-dependent modulation of vasoconstriction.

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