BK通道
甲氧沙明
哇巴因
化学
伊比利亚毒素
血管平滑肌
原癌基因酪氨酸蛋白激酶Src
细胞生物学
Rho相关蛋白激酶
内科学
内分泌学
激酶
钾通道
生物化学
生物
膜电位
医学
受体
有机化学
钠
兴奋剂
平滑肌
作者
Travis Orth,Anastasia Pyanova,Samuel E. Lux,Peter Kaiser,Isabel Reinheimer,Daniel Løgstrup Nielsen,Josef Ali Khalid,Salomé Rognant,Thomas A. Jepps,Vladimir V. Matchkov,Rudolf Schubert
标识
DOI:10.1096/fj.202400628rr
摘要
Abstract Large‐conductance, calcium‐activated potassium channels (BK channels) and the Na/K‐ATPase are expressed universally in vascular smooth muscle. The Na/K‐ATPase may act via changes in the intracellular Ca 2+ concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels. Whether BK channels functionally interact in vascular smooth muscle cells with the Na/K‐ATPase remains to be elucidated. Thus, this study addressed the hypothesis that BK channels limit ouabain‐induced vasocontraction. Rat mesenteric arteries were studied using isometric myography, FURA‐2 fluorimetry and proximity ligation assay. The BK channel blocker iberiotoxin potentiated methoxamine‐induced contractions. The cardiotonic steroid, ouabain (10 −5 M), induced a contractile effect of IBTX at basal tension prior to methoxamine administration and enhanced the pro‐contractile effect of IBTX on methoxamine‐induced contractions. These facilitating effects of ouabain were prevented by the inhibition of either NCX or Src kinase. Furthermore, inhibition of NCX or Src kinase reduced the BK channel‐mediated negative feedback regulation of arterial contraction. The effects of NCX and Src kinase inhibition were independent of each other. Co‐localization of the Na/K‐ATPase and the BK channel was evident. Our data suggest that BK channels limit ouabain‐induced vasocontraction by a dual mechanism involving the NCX and Src kinase signaling. The data propose that the NCX and the Src kinase pathways, mediating the ouabain‐induced activation of the BK channel, act in an independent manner.
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