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

Heppner, Thomas J., Adrian D. Bonev, L. Fernando Santana, and Mark T. Nelson. Alkaline pH shifts Ca2 sparks to Ca2 waves in smooth muscle cells of pressurized cerebral arteries. Am J Physiol Heart Circ Physiol 283: H2169–H2176, 2002; 10.1152/ajpheart.00603.2002.—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.