Alkaline pH shifts Ca2+ sparks to Ca2+waves in smooth muscle cells of pressurized cerebral arteries

Abstract

The effects of external pH (7.0–8.0) on intracellular Ca2+ signals (Ca2+ sparks and Ca2+ waves) were examined in smooth muscle cells from intact pressurized arteries from rats. Elevating the external pH from 7.4 to 7.5 increased the frequency of local, Ca2+transients, or “Ca2+ sparks,” and, at pH 7.6, significantly increased the frequency of Ca2+ waves. Alkaline pH-induced Ca2+ waves were inhibited by blocking Ca2+ release from ryanodine receptors but were not prevented by inhibitors of voltage-dependent Ca2+ channels, phospholipase C, or inositol 1,4,5-trisphosphate receptors. Activating ryanodine receptors with caffeine (5 mM) at pH 7.4 also induced repetitive Ca2+ waves. Alkalization from pH 7.4 to pH 7.8–8.0 induced a rapid and large vasoconstriction. Approximately 82% of the alkaline pH-induced vasoconstriction was reversed by inhibitors of voltage-dependent Ca2+ channels. The remaining constriction was reversed by inhibition of ryanodine receptors. These findings indicate that alkaline pH-induced Ca2+ waves originate from ryanodine receptors and make a minor, direct contribution to alkaline pH-induced vasoconstriction.