scholarly journals Peripheral Coupling Sites Formed by STIM1 Govern the Contractility of Vascular Smooth Muscle Cells

2021 ◽  
Author(s):  
Vivek Krishnan ◽  
Sher Ali ◽  
Albert L. Gonzales ◽  
Pratish Thakore ◽  
Caoimhin S. Griffin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Transmembrane Domain ◽  
Muscle Cells ◽  
Channel Activity ◽  
Resistance Arteries ◽  
Store Depletion ◽  
Domain Protein

Peripheral coupling between the sarcoplasmic reticulum (SR) and plasma membrane (PM) forms signaling complexes that regulate the membrane potential and contractility of vascular smooth muscle cells (VSMCs), although the mechanisms responsible for these membrane interactions are poorly understood. In many cells, STIM1 (stromal interaction molecule 1), a single transmembrane-domain protein that resides in the endoplasmic reticulum (ER), transiently moves to ER-PM junctions in response to depletion of ER Ca2+ stores and initiates store-operated Ca2+ entry (SOCE). Fully differentiated VSMCs express STIM1 but exhibit only marginal SOCE activity. We hypothesized that STIM1 is constitutively active in contractile VSMCs and maintains peripheral coupling. In support of this concept, we found that the number and size of SR-PM interacting sites were decreased and SR-dependent Ca2+ signaling processes were disrupted in freshly isolated cerebral artery SMCs from tamoxifen-inducible, SMC specific STIM1-knockout (Stim1-smKO) mice. VSMCs from Stim1-smKO mice also exhibited a reduction in nanoscale colocalization between Ca2+-release sites on the SR and Ca2+-activated ion channels on the PM, accompanied by diminished channel activity. Stim1-smKO mice were hypotensive and resistance arteries isolated from them displayed blunted contractility. These data suggest that STIM1 – independent of SR Ca2+ store depletion – is critically important for stable peripheral coupling in contractile VSMCs.

scholarly journals TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure

2009 ◽  
Vol 297 (3) ◽  
pp. H1096-H1102 ◽  
Author(s):  
Scott Earley ◽  
Thierry Pauyo ◽  
Rebecca Drapp ◽  
Matthew J. Tavares ◽  
Wolfgang Liedtke ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Peripheral Resistance ◽  
Muscle Cells ◽  
Mesenteric Arteries ◽  
Transient Receptor Potential Vanilloid ◽  
Resistance Arteries

Transient receptor potential vanilloid 4 (TRPV4) channels have been implicated as mediators of calcium influx in both endothelial and vascular smooth muscle cells and are potentially important modulators of vascular tone. However, very little is known about the functional roles of TRPV4 in the resistance vasculature or how these channels influence hemodynamic properties. In the present study, we examined arterial vasomotor activity in vitro and recorded blood pressure dynamics in vivo using TRPV4 knockout (KO) mice. Acetylcholine-induced hyperpolarization and vasodilation were reduced by ∼75% in mesenteric resistance arteries from TRPV4 KO versus wild-type (WT) mice. Furthermore, 11,12-epoxyeicosatrienoic acid (EET), a putative endothelium-derived hyperpolarizing factor, activated a TRPV4-like cation current and hyperpolarized the membrane of vascular smooth muscle cells, resulting in the dilation of mesenteric arteries from WT mice. In contrast, 11,12-EET had no effect on membrane potential, diameter, or ionic currents in the mesenteric arteries from TRPV4 KO mice. A disruption of the endothelium reduced 11,12-EET-induced hyperpolarization and vasodilatation by ∼50%. A similar inhibition of these responses was observed following the block of endothelial (small and intermediate conductance) or smooth muscle (large conductance) K+ channels, suggesting a link between 11,12-EET activity, TRPV4, and K+ channels in endothelial and smooth muscle cells. Finally, we found that hypertension induced by the inhibition of nitric oxide synthase was greater in TRPV4 KO compared with WT mice. These results support the conclusion that both endothelial and smooth muscle TRPV4 channels are critically involved in the vasodilation of mesenteric arteries in response to endothelial-derived factors and suggest that in vivo this mechanism opposes the effects of hypertensive stimuli.

scholarly journals Proteoglycan Production by Vascular Smooth Muscle Cells From Resistance Arteries of Hypertensive Rats

Hypertension ◽  
1999 ◽  
Vol 34 (4) ◽  
pp. 893-896 ◽  
Author(s):  
Claudia Magdalena Castro ◽  
Montserrat Cecilia Cruzado ◽  
Roberto Miguel Miatello ◽  
Norma Raquel Risler
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Resistance Arteries ◽  
Hypertensive Rats

Abstract P1120: Opioids Induce Proliferation in Vascular Smooth Muscle Cells Leading to an Increase in Myogenic Tone in Resistance Arteries

Hypertension ◽  
2019 ◽  
Vol 74 (Suppl_1) ◽  
Author(s):  
Jeremy C Tomcho ◽  
Jonnelle Edwards ◽  
Nicole R Bearss ◽  
Cameron G McCarthy ◽  
Bina Joe ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Myogenic Tone ◽  
Resistance Arteries

scholarly journals Bcl-2 decreases voltage-gated K+channel activity and enhances survival in vascular smooth muscle cells

2001 ◽  
Vol 281 (1) ◽  
pp. C157-C165 ◽  
Author(s):  
Daryoush Ekhterae ◽  
Oleksandr Platoshyn ◽  
Stefanie Krick ◽  
Ying Yu ◽  
Sharon S. McDaniel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Channel Activity ◽  
Voltage Gated ◽  
Kv Channel ◽  
Kv Channels ◽  
Volume Decrease

Cell shrinkage is an incipient hallmark of apoptosis in a variety of cell types. The apoptotic volume decrease has been demonstrated to attribute, in part, to K+efflux; blockade of plasmalemmal K+channels inhibits the apoptotic volume decrease and attenuates apoptosis. Using combined approaches of gene transfection, single-cell PCR, patch clamp, and fluorescence microscopy, we examined whether overexpression of Bcl-2, an anti-apoptotic oncoprotein, inhibits apoptosis in pulmonary artery smooth muscle cells (PASMC) by diminishing the activity of voltage-gated K+(Kv) channels. A human bcl-2gene was infected into primary cultured rat PASMC using an adenoviral vector. Overexpression of Bcl-2 significantly decreased the amplitude and current density of Kv currents ( IKv). In contrast, the apoptosis inducer staurosporine (ST) enhanced IKv. In bcl-2-infected cells, however, the ST-induced increase in IKvwas completely abolished, and the ST-induced apoptosis was significantly inhibited compared with cells infected with an empty adenovirus (− bcl-2). Blockade of Kv channels in control cells (− bcl-2) by 4-aminopyridine also inhibited the ST-induced increase in IKvand apoptosis. Furthermore, overexpression of Bcl-2 accelerated the inactivation of IKvand downregulated the mRNA expression of the pore-forming Kv channel α-subunits (Kv1.1, Kv1.5, and Kv2.1). These results suggest that inhibition of Kv channel activity may serve as an additional mechanism involved in the Bcl-2-mediated anti-apoptotic effect on vascular smooth muscle cells.

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