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

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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.