Ca2+ ions can affect intracellular pH in mammalian cardiac muscle

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Abstract
Although intracellular pH (pHi) has important effects on both the mechanical and electrical properties of cardiac muscle1–3, the control of pHi in the heart is still poorly understood. One important determinant of pHi appears to be the transmembrane Na+ gradient4,5. It has therefore been suggested that Na+–H+ exchange assists in the control of pHi in heart as has been proposed for other excitable cells6–8. However, pHi and the intracellular Ca2+ concentration ([Ca2+]i) are interdependent in a variety of tissues9–11 and it has been shown recently that pHi can affect [Ca2+]i in cardiac muscle5,12. As [Ca2+]i in cardiac muscle is also strongly influenced by the transmembrane Na+ gradient5 it is possible that the apparent Na+ -dependence of pHi is secondary to changes in [Ca2+]i. Previous work in cardiac muscle has not been able to separate the effects of Na+–H+ exchange and [Ca2+]i on pHi (refs 4, 5). Here we demonstrate in cardiac muscle that an increase in [Ca2+]i produces an intracellular acidification which cannot be ascribed to Na+–H+ exchange.