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Extracellular acidosis contracts coronary but neither renal nor mesenteric artery via modulation of H + ,K + ‐ATPase, voltage‐gated K + channels and L‐type Ca 2+ channels
Author(s) -
Niu Longgang,
Liu Yu,
Hou Xiaomin,
Cui Lijuan,
Li Jiangtao,
Zhang Xuanping,
Zhang Mingsheng
Publication year - 2014
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2014.078634
Subject(s) - acidosis , extracellular , medicine , endocrinology , membrane potential , chemistry , physics , biochemistry
New FindingsWhat is the central question of this study? We asked whether there are any differences in responses to extracellular acidosis among arteries of different origin and whether K + channels, Ca 2+ channels and H + ,K + ‐ATPase are involved in extracellular acidosis‐induced coronary myogenic responses.What is the main finding and its importance? This report is the first to demonstrate that extracellular acidosis alkalinizes the cytosol of arterial smooth muscle cells freshly isolated from rat coronary artery and contracts the artery exclusively and to suggest that modulation of voltage‐gated K + channels, voltage‐gated Ca 2+ channels and H + ,K + ‐ATPase are involved in the contraction.Extracellular acidosis (EA) jeopardizes the heart, whereas mild extracellular alkalinization is cardioprotective, but it remains elusive how the coronary artery (CA) responses to EA. In the present study, EA was demonstrated to induce contraction in rat coronary artery (RCA) in a manner dependent on extracellular pH (pH o , 7.2–6.6), whereas it did not affect the resting tone of either rat renal interlobe artery (RIA) or mesenteric artery (MA). The amplitude of contraction provoked by pH o 6.8 was approximately equal to that induced by 60 mmol l −1 KCl at pH o 7.4. Blockade of L‐type voltage‐gated Ca 2+ channels and inhibition of H + ,K + ‐ATPase attenuated the contraction, whereas inhibition of nitric oxide synthesis and endothelial denudation augmented it. A molecular probe study showed that EA acidified the cytosol of arterial smooth muscle cells (ASMCs) in RIA and MA, but alkalinized it in RCA. Extracellular acidosis elevated the intracellular Ca 2+ concentration exclusively in RCA ASMCs. Patch‐clamp studies showed that EA enhanced L‐type voltage‐gated Ca 2+ channel currents in RCA ASMCs, but depressed the currents in MA ASMCs and did not affect the currents in RIA ASMCs. Extracellular acidosis depressed voltage‐gated K + channel (K V ) currents only in RCA ASMCs. Lansoprazole blunted all these observed effects of EA on RCA. Taken together, the present results demonstrate that the responses of RCA to EA are different from those of RIA and MA and suggest that activation of L‐type voltage‐gated Ca 2+ channels and H + ,K + ‐ATPase as well as depression of K V may, at least partly, underlie the EA‐induced contraction in RCA.