Mechanisms underlying regional differences in the Ca<sup>2+</sup> sensitivity of BK<sub>Ca</sub> current in arteriolar smooth muscle

Yang, Yan; Saito, Yoshiro; Nourian, Zahra; Ella, Srikanth R.; Li, Min; Stupica, Aaron J.; Korthuis, Ronald J.; Davis, Michael J.; Braun, Andrew P.; Hill, Michael A.

doi:10.1113/jphysiol.2012.241562

Cited by 39 publications

(45 citation statements)

References 35 publications

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“…VSMCs exhibit heterogeneity in BK Ca activity or their sensitivity that may contribute to tissue-specific differences in the regulation of myogenic vasoconstriction (525,618,1632). For example, the BK Ca is more sensitive to increased [Ca 2ϩ ] i resulting from Ca 2ϩ sparks generated by Ca 2ϩ release from sarcoplasmic reticulum in cerebral than skeletal muscle cremaster arteries.…”

Section: B Potassium Channelsmentioning

confidence: 97%

“…For example, the BK Ca is more sensitive to increased [Ca 2ϩ ] i resulting from Ca 2ϩ sparks generated by Ca 2ϩ release from sarcoplasmic reticulum in cerebral than skeletal muscle cremaster arteries. The resultant vasodilation attenuated myogenic vasoconstriction in cerebral arteries (1632). The variation in sensitivity might be explained by the number of ␤ 1 subunits of the BK Ca channel (1632).…”

Section: B Potassium Channelsmentioning

confidence: 99%

“…The resultant vasodilation attenuated myogenic vasoconstriction in cerebral arteries (1632). The variation in sensitivity might be explained by the number of ␤ 1 subunits of the BK Ca channel (1632).…”

Section: B Potassium Channelsmentioning

confidence: 99%

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Renal Autoregulation in Health and Disease

Carlström

Wilcox

Arendshorst

2015

Physiological Reviews

391

383

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Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80-180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca(2+)]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca(2+)]i occurs predominantly by Ca(2+) influx through L-type voltage-operated Ca(2+) channels (VOCC). Increased [Ca(2+)]i activates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca(2+) from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca(2+) sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism. Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study.

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Section: B Potassium Channelsmentioning

confidence: 97%

Section: B Potassium Channelsmentioning

confidence: 99%

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Renal Autoregulation in Health and Disease

Carlström

Wilcox

Arendshorst

2015

Physiological Reviews

391

383

View full text Add to dashboard Cite

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“…A previous study using rats has documented a higher functional expression of BK β1 in cerebral artery (territory unspecified) arterioles vs. primary and secondary branches of cremaster artery [91]. Likewise, smooth muscle BK channels in C57/BL6 mouse cerebral arteries show a higher functional presence of BK β1 when compared to pulmonary artery myocytes [94].…”

Section: Discussionmentioning

confidence: 99%

Differential distribution and functional impact of BK channel beta1 subunits across mesenteric, coronary, and different cerebral arteries of the rat

Kuntamallappanavar

Bisen

Bukiya

et al. 2016

Pflugers Arch - Eur J Physiol

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Large conductance, Ca2+i- and voltage-gated K+ (BK) channels regulate myogenic tone and thus, arterial diameter. In smooth muscle (SM), BK channels include channel-forming α and auxiliary β1 subunits. BK β1 increases the channel’s Ca2+ sensitivity allowing BK channels to negatively feed-back on depolarization-induced Ca2+-entry, oppose SM contraction and favor vasodilation. Thus, endothelial-independent vasodilation can be evoked though targeting of SM BK β1 by endogenous ligands, including lithocholate (LCA). Here, we investigated the expression of BK β1 across arteries of the cerebral and peripheral circulations, and the contribution of such expression to channel function and BK β1–mediated vasodilation. Data demonstrate that endothelium-independent, BK β1-mediated vasodilation by LCA is larger in coronary (CA) and basilar (BA) arteries than in anterior cerebral (ACA), middle cerebral (MCA), posterior cerebral (PCA), and mesenteric (MA) arteries, all arterial segments having a similar diameter. Thus, differential dilation occurs in extracranial arteries which are subjected to similar vascular pressure (CA vs. MA), and in arteries that irrigate different brain regions (BA vs. ACA, MCA, PCA). SM BK channels from BA and CA displayed increased basal activity and LCA responses, indicating increased BK β1 functional presence. Indeed, in the absence of detectable changes in BK α, BA and CA myocytes showed an increased location of BK β1 in the plasmalemma/subplasmalemma. Moreover, these myocytes distinctly showed increased BK β1 mRNA levels. Supporting a major role of enhanced BK β1 transcripts in artery dilation, LCA-induced dilation of MCA transfected with BK β1 cDNA was as high as LCA-induced dilation of untransfected BA or CA.

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“…For example, cerebral artery myocyte BK channels have a higher β1:α subunit ratio than cremaster artery myocytes, elevating their Ca 2+ -sensitivity. 36 As γ and β1 subunits interact to modulate BK channels, variable expression of each subunit may fine tune and customize BK channel voltage-and Ca 2+ -sensitivity in myocytes of different vascular beds. Hypertension is associated with a decrease in β1 expression and function in arterial myocytes, leading to a reduction in BK channel activity and vasoconstriction.…”

Section: Discussionmentioning

confidence: 99%

LRRC26 Is a Functional BK Channel Auxiliary γ Subunit in Arterial Smooth Muscle Cells

Evanson

Bannister

Leo

et al. 2014

Circulation Research

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Rationale Smooth muscle cell (myocyte) large-conductance calcium (Ca2+)-activated potassium (BK) channels are functionally significant modulators of arterial contractility. Arterial myocytes express both pore-forming BKα and auxiliary β1 subunits, which increase channel Ca2+-sensitivity. Recently, several leucine-rich repeat containing (LRRC) proteins have been identified as auxiliary γ subunits that elevate the voltage-sensitivity of recombinant and prostate adenocarcinoma BK channels. LRRC expression and physiological functions in native cell types are unclear. Objective Investigate the expression and physiological functions of LRRC26 in arterial myocytes. Methods and Results RT-PCR and Western blotting detected LRRC26 mRNA and protein in cerebral artery myocytes. Biotinylation, immunofluorescence resonance energy transfer microscopy and co-immunoprecipitation indicated that LRRC26 was located in close spatial proximity to, and associated with, plasma membrane BKα subunits. LRRC26 knockdown (RNAi) reduced total and surface LRRC26, but did not alter BKα or β1, proteins in arteries. LRRC26 knockdown did not alter Ca2+ sparks, but reduced BK channel voltage-sensitivity, which reduced channel apparent Ca2+-sensitivity and transient BK current frequency and amplitude in myocytes. LRRC26 knockdown also increased myogenic tone over a range (40 – 100 mmHg) of intravascular pressures, and reduced vasoconstriction to iberiotoxin and vasodilation to NS1619, BK channel inhibitors and activators, respectively. In contrast, LRRC26 knockdown did not alter depolarization (60 mmol/L K+)-induced vasoconstriction. Conclusions LRRC26 is expressed, associates with BKα subunits, and elevates channel voltage- and apparent Ca2+-sensitivity in arterial myocytes to induce vasodilation. This study indicates that arterial myocytes express a functional BK channel γ subunit.

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Mechanisms underlying regional differences in the Ca²⁺ sensitivity of BK_Ca current in arteriolar smooth muscle

Cited by 39 publications

References 35 publications

Renal Autoregulation in Health and Disease

Renal Autoregulation in Health and Disease

Differential distribution and functional impact of BK channel beta1 subunits across mesenteric, coronary, and different cerebral arteries of the rat

LRRC26 Is a Functional BK Channel Auxiliary γ Subunit in Arterial Smooth Muscle Cells

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Mechanisms underlying regional differences in the Ca2+ sensitivity of BKCa current in arteriolar smooth muscle

Cited by 39 publications

References 35 publications

Renal Autoregulation in Health and Disease

Renal Autoregulation in Health and Disease

Differential distribution and functional impact of BK channel beta1 subunits across mesenteric, coronary, and different cerebral arteries of the rat

LRRC26 Is a Functional BK Channel Auxiliary γ Subunit in Arterial Smooth Muscle Cells

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Mechanisms underlying regional differences in the Ca²⁺ sensitivity of BK_Ca current in arteriolar smooth muscle