Extracellular acidosis contracts coronary but neither renal nor mesenteric artery via modulation of H+,K+-ATPase, voltage-gated K+ channels and L-type Ca2+ channels.

Abstract

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 (pHo, 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 pHo6.8 was approximately equal to that induced by 60mmoll(-1) KCl at pHo7.4. 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 (KV) 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 KV may, at least partly, underlie the EA-induced contraction in RCA.