scholarly journals Increased amplitude of inward rectifier K+ currents with advanced age in smooth muscle cells of murine superior epigastric arteries

2017 ◽  
Vol 312 (6) ◽  
pp. H1203-H1214 ◽  
Author(s):  
Sebastien Hayoz ◽  
Jessica Pettis ◽  
Vanessa Bradley ◽  
Steven S. Segal ◽  
William F. Jackson
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Functional Expression ◽  
Flow Regulation ◽  
Advanced Age ◽  
Vasomotor Tone ◽  
Blood Flow Regulation ◽  
Old Mice

Inward rectifier K+ channels (KIR) may contribute to skeletal muscle blood flow regulation and adapt to advanced age. Using mouse abdominal wall superior epigastric arteries (SEAs) from either young (3–6 mo) or old (24–26 mo) male C57BL/6 mice, we investigated whether SEA smooth muscle cells (SMCs) express functional KIR channels and how aging may affect KIR function. Freshly dissected SEAs were either enzymatically dissociated to isolate SMCs for electrophysiological recording (perforated patch) and mRNA expression or used intact for pressure myography. With 5 mM extracellular K+ concentration ([K+]o), exposure of SMCs to the KIR blocker Ba2+ (100 μM) had no significant effect ( P > 0.05) on whole cell currents elicited by membrane potentials spanning −120 to −30 mV. Raising [K+]o to 15 mM activated Ba2+-sensitive KIR currents between −120 and −30 mV, which were greater in SMCs from old mice than in SMCs from young mice ( P < 0.05). Pressure myography of SEAs revealed that while aging decreased maximum vessel diameter by ~8% ( P < 0.05), it had no significant effect on resting diameter, myogenic tone, dilation to 15 mM [K+]o, Ba2+-induced constriction in 5 mM [K+]o, or constriction induced by 15 mM [K+]o in the presence of Ba2+ ( P > 0.05). Quantitative RT-PCR revealed SMC expression of KIR2.1 and KIR2.2 mRNA that was not affected by age. Barium-induced constriction of SEAs from young and old mice suggests an integral role for KIR in regulating resting membrane potential and vasomotor tone. Increased functional expression of KIR channels during advanced age may compensate for other age-related changes in SEA function. NEW & NOTEWORTHY Ion channels are integral to blood flow regulation. We found greater functional expression of inward rectifying K+ channels in smooth muscle cells of resistance arteries of mouse skeletal muscle with advanced age. This adaptation to aging may contribute to the maintenance of vasomotor tone and blood flow regulation during exercise.

scholarly journals Microvascular mechanisms limiting skeletal muscle blood flow with advancing age

2018 ◽  
Vol 125 (6) ◽  
pp. 1851-1859 ◽  
Author(s):  
Matthew J. Socha ◽  
Steven S. Segal
Keyword(s):  
Hydrogen Peroxide ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Blood Flow ◽  
Muscle Cells ◽  
Advanced Age ◽  
Feed Arteries ◽  
Young Mice

Effective oxygen delivery to active muscle fibers requires that vasodilation initiated in distal arterioles, which control flow distribution and capillary perfusion, ascends the resistance network into proximal arterioles and feed arteries, which govern total blood flow into the muscle. With exercise onset, ascending vasodilation reflects initiation and conduction of hyperpolarization along endothelium from arterioles into feed arteries. Electrical coupling of endothelial cells to smooth muscle cells evokes the rapid component of ascending vasodilation, which is sustained by ensuing release of nitric oxide during elevated luminal shear stress. Concomitant sympathetic neural activation inhibits ascending vasodilation by stimulating α-adrenoreceptors on smooth muscle cells to constrict the resistance vasculature. We hypothesized that compromised muscle blood flow in advanced age reflects impaired ascending vasodilation through actions on both cell layers of the resistance network. In the gluteus maximus muscle of old (24 mo) vs. young (4 mo) male mice (corresponding to mid-60s vs. early 20s in humans) inhibition of α-adrenoreceptors in old mice restored ascending vasodilation, whereas even minimal activation of α-adrenoreceptors in young mice attenuated ascending vasodilation in the manner seen with aging. Conduction of hyperpolarization along the endothelium is impaired in old vs. young mice because of “leaky” membranes resulting from the activation of potassium channels by hydrogen peroxide released from endothelial cells. Exposing the endothelium of young mice to hydrogen peroxide recapitulates this effect of aging. Thus enhanced α-adrenoreceptor activation of smooth muscle in concert with electrically leaky endothelium restricts muscle blood flow by impairing ascending vasodilation in advanced age.

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

Physiology ◽  
1992 ◽  
Vol 7 (4) ◽  
pp. 152-156 ◽  
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.

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

2020 ◽  
Vol 16 (5) ◽  
pp. 502-515 ◽  
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.

Endothelial and smooth muscle cell conduction in arterioles controlling blood flow

1998 ◽  
Vol 274 (1) ◽  
pp. H178-H186 ◽  
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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