ISSN:
1432-2013
Keywords:
Key words Acidosis
;
Smooth muscle
;
Coronary artery
;
Ca2+-activated K+ channels
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Although acidosis induces vasodilation, the vascular responses mediated by large-conductance Ca2+-activated K+ (KCa) channels have not been investigated in coronary artery smooth muscle cells. We therefore investigated the response of porcine coronary arteries and smooth muscle cells to acidosis, as well as the role of KCa channels in the regulation of muscular tone. Acidosis (pH 7.3–6.8), produced by adding HCl to the extravascular solution, elicited concentration-dependent relaxation of precontracted, endothelium-denuded arterial rings. Glibenclamide (20 µM) significantly inhibited the vasodilatory response to acidosis (pH 7.3-6.8). Charybdotoxin (100 nM) was effective only at pH 6.9–6.8. When we exposed porcine coronary artery smooth muscle cells to a low-pH solution, KCa channel activity in cell-attached patches increased. However, pretreatment of these cells with 10 or 30 µM O, O′-bis(2-aminophenyl)ethyleneglycol-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl)ester (BAPTA-AM), a Ca2+ chelator for which the cell membrane is permeable, abolished the H+-mediated activation of KCa channels in cell-attached patches. Under these circumstances H+ actually inhibited KCa channel activity. When inside-out patches were exposed to a [Ca2+] of 10–6 M [adjusted with ethyleneglycolbis(β-aminoethylester)-N,N,N′,N′-tetraacetic acid (EGTA) at pH 7.3], KCa channels were activated by H+ concentration dependently. However, when these patches were exposed to a [Ca2+] of 10–6 M adjusted with BAPTA at pH 7.3, H+ inhibited KCa channel activity. Extracellular acidosis had no significant direct effect on KCa channels, suggesting that extracellular H+ exerts its effects after transport into the cell, and that KCa channels are regulated by intracellular H+ and by cytosolic free Ca2+ modulated by acute acidosis. These results indicate that the modulation of KCa channel kinetics by acidosis plays an important role in the determination of membrane potential and, hence, coronary arterial tone.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004240050665
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