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Abstract

Cell stimulation raises the cytosolic free Ca²⁺ concentration, [Ca²⁺]_i, and induces activation of Na⁺/H⁺ exchange which raises the cytosolic pH, pH_i. Recent studies have addressed the question whether Na⁺/H⁺ exchange plays a role in Ca²⁺ influx and, specifically, whether a rise in pH_i alone suffices to open Ca²⁺ channels in the plasma membrane. Artificial cytosolic alkalinization can induce Ca²⁺ uptake across the plasma membrane of endothelial cells, lymphocytes and smooth muscle cells. Furthermore, inhibition of Na⁺/H⁺ exchange reduces aganist-induced ²⁺ influx in endothelial cells and platelets which supports the concept that pH_i may regulate the opening of Ca²⁺ channels in the plasma membrane. Although these findings argue in favour of a role of Na⁺/H⁺ exchange in Ca²⁺ influx, the onset of pH_i and Ca²⁺ rises, measured with fluorescent indicators, suggests that the increase in [Ca²⁺]_i distinctly precedes the increase in pH_i. This challenges the concept that alkalinization per se is a sufficient signal for the opening of Ca²⁺ channels in the plasma membrane.