Current perspective on differential communication in small resistance arteriesThis article is part of a Special Issue on Information Transfer in the Microcirculation.

Blood flow is controlled by an integrated network of resistance arteries that are coupled in series and parallel with one another. To dramatically alter tissue perfusion as required during periods of high metabolic demand, arterial networks must dilate in a coordinated manner. Gap junctions facilitate arterial coordination by enabling electrical stimuli to conduct among endothelial and (or) smooth muscle cells. The goal of this review was to provide an introduction to the field of vascular communication, the process of intercellular conduction, and the manner in which key properties influence charge flow. After a brief historical introduction, we establish the idea that electrical stimuli conduct differentially among neighbouring endothelial and smooth muscle cells. Highlighting recent studies that have synergistically combined computational and experimental approaches, this perspective explores how specific structural, electrical, and gap junctional properties enable electrical phenomenon to conduct differentially. To close, the concept of differential communication is functionally integrated into a mechanistic understanding of blood flow control.

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Communication Among Endothelial and Smooth Muscle Cells Coordinates Blood Flow Control During Exercise

Physiology ◽

10.1152/physiologyonline.1992.7.4.152 ◽

1992 ◽

Vol 7 (4) ◽

pp. 152-156 ◽

Cited By ~ 6

Author(s):

SS Segal

Keyword(s):

Blood Flow ◽

Smooth Muscle ◽

Endothelial Cell ◽

Locus Of Control ◽

Smooth Muscle Cells ◽

Flow Control ◽

Muscle Cells ◽

Peripheral Blood Flow ◽

Metabolic Demand ◽

Blood Flow Control

Peripheral blood flow control during exercise is coordinated among several vascular locations. The locus of control shifts upstream from distal arterioles into feeding arteries as metabolic demand increases. This shift occurs by cell-to-cell conduction and by flow-dependent endothelial cell-mediated relaxation of smooth muscle cells.

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GTP-binding (G) protein carboxyl methylation controls agonist-induced intracellular Ca2+ response in rat resistance arteries and aortic vascular smooth muscle cells (VSMC).

American Journal of Hypertension ◽

10.1016/0895-7061(96)81545-7 ◽

1996 ◽

Vol 9 (4) ◽

pp. 34A

Author(s):

J ROULLET

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

G Protein ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Resistance Arteries ◽

Carboxyl Methylation ◽

Gtp Binding

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Caveolin-1 and caveolin-3 regulate Ca2+ homeostasis of single smooth muscle cells from rat cerebral resistance arteries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00669.2006 ◽

2007 ◽

Vol 293 (1) ◽

pp. H204-H214 ◽

Cited By ~ 12

Author(s):

T. Kamishima ◽

T. Burdyga ◽

J. A. Gallagher ◽

J. M. Quayle

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Removal Rate ◽

Muscle Cells ◽

Amino Acid Residues ◽

Resistance Arteries ◽

Inhibitory Peptide ◽

Caveolin 1 ◽

Domain Peptide ◽

Cerebral Resistance

The role of caveolins, signature proteins of caveolae, in arterial Ca2+ regulation is unknown. We investigated modulation of Ca2+ homeostasis by caveolin-1 and caveolin-3 using smooth muscle cells from rat cerebral resistance arteries. Membrane current and Ca2+ transients were simultaneously measured with voltage-clamped single cells. Membrane depolarization triggered Ca2+ current and increased intracellular Ca2+ concentration ([Ca2+]i). After repolarization, elevated [Ca2+]i returned to the resting level. Ca2+ removal rate was determined from the declining phase of the Ca2+ transient. Application of caveolin-1 antibody or caveolin-1 scaffolding domain peptide, corresponding to amino acid residues 82–101 of caveolin-1, significantly slowed Ca2+ removal rate at a measured [Ca2+]i of 250 nM, with little effect at a measured [Ca2+]i of 600 nM. Application of caveolin-3 antibody or caveolin-3 scaffolding domain peptide, corresponding to amino acid residues 55–74 of caveolin-3, also significantly slowed Ca2+ removal rate at a measured [Ca2+]i of 250 nM, with little effect at a measured [Ca2+]i of 600 nM. Likewise, application of calmodulin inhibitory peptide, autocamtide-2-related inhibitory peptide, and cyclosporine A, inhibitors for calmodulin, Ca2+/calmodulin-dependent protein kinase II, and calcineurin, also significantly inhibited Ca2+ removal rate at a measured [Ca2+]i of 250 nM but not at 600 nM. Application of cyclopiazonic acid, a sarcoplasmic reticulum Ca2+ ATPase inhibitor, also significantly inhibited Ca2+ removal rate at a measured [Ca2+]i of 250 nM but not at 600 nM. Our results suggest that caveolin-1 and caveolin-3 are important in Ca2+ removal of resistance artery smooth muscle cells.

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Sodium-potassium pump current in smooth muscle cells from mesenteric resistance arteries of the guinea-pig

The Journal of Physiology ◽

10.1111/j.1469-7793.1999.0203o.x ◽

1999 ◽

Vol 519 (1) ◽

pp. 203-212 ◽

Cited By ~ 27

Author(s):

Yoshito Nakamura ◽

Yusuke Ohya ◽

Isao Abe ◽

Masatoshi Fujishima

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

Pump Current ◽

Resistance Arteries ◽

Sodium Potassium ◽

Sodium Potassium Pump

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TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00241.2009 ◽

2009 ◽

Vol 297 (3) ◽

pp. H1096-H1102 ◽

Cited By ~ 132

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.

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

10.1101/2021.05.25.445565 ◽

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.

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The Neurovascular Unit: Focus on the Regulation of Arterial Smooth Muscle Cells

Current Neurovascular Research ◽

10.2174/1567202616666191026122642 ◽

2020 ◽

Vol 16 (5) ◽

pp. 502-515 ◽

Cited By ~ 1

Author(s):

Patrícia Quelhas ◽

Graça Baltazar ◽

Elisa Cairrao

Keyword(s):

Blood Flow ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Blood Vessels ◽

Neurovascular Unit ◽

Muscle Cells ◽

Cerebral Blood Vessels ◽

Mural Cells ◽

Brain Pericytes ◽

The Brain

The neurovascular unit is a physiological unit present in the brain, which is constituted by elements of the nervous system (neurons and astrocytes) and the vascular system (endothelial and mural cells). This unit is responsible for the homeostasis and regulation of cerebral blood flow. There are two major types of mural cells in the brain, pericytes and smooth muscle cells. At the arterial level, smooth muscle cells are the main components that wrap around the outside of cerebral blood vessels and the major contributors to basal tone maintenance, blood pressure and blood flow distribution. They present several mechanisms by which they regulate both vasodilation and vasoconstriction of cerebral blood vessels and their regulation becomes even more important in situations of injury or pathology. In this review, we discuss the main regulatory mechanisms of brain smooth muscle cells and their contributions to the correct brain homeostasis.

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Endothelial and smooth muscle cell conduction in arterioles controlling blood flow

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.274.1.h178 ◽

1998 ◽

Vol 274 (1) ◽

pp. H178-H186 ◽

Cited By ~ 70

Author(s):

Donald G. Welsh ◽

Steven S. Segal

Keyword(s):

Blood Flow ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Lucifer Yellow ◽

Muscle Cells ◽

Cheek Pouch ◽

Electrophysiological Recordings ◽

Cell Layers

We performed intracellular recording with Lucifer yellow dye microinjection to investigate the cellular pathway(s) by which constriction and dilation are conducted along the wall of arterioles (diameter 47 ± 1 μm, n = 63) supplying blood flow to the cheek pouch of anesthetized hamsters. At rest, membrane potential ( E m) of endothelial (−36 ± 1 mV) and smooth muscle (−35 ± 1 mV) cells was not different. Micropipette delivery of norepinephrine (NE) or phenylephrine (PE) produced smooth muscle cell depolarization (5–41 mV) and vasoconstriction (7–49 μm) at the site of release and along the arteriole with no effect on E m of endothelial cells. KCl produced conduction of depolarization and vasoconstriction with similar electrical kinetics in endothelial and smooth muscle cells. Acetylcholine triggered conduction of vasodilation (2–25 μm) and hyperpolarization (3–33 mV) along both cell layers; in smooth muscle, this change in E m was prolonged and followed by a transient depolarization. These cell-specific electrophysiological recordings uniquely illustrate that depolarization and constriction are initiated and conducted along smooth muscle, independent of the endothelium. Furthermore, conduction of vasodilation is explained by the spread of hyperpolarization along homologously coupled endothelial and smooth muscle cells, with distinctive responses between cell layers. The discontinuity between endothelium and smooth muscle indicates that these respective pathways are not electrically coupled during blood flow control.

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