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Free keywords:
platelet; Endothelial cell; Lymphocyte; Smooth muscle cell; Na+/H+ exchange
Abstract:
Cell stimulation raises the cytosolic free Ca2+ concentration, [Ca2+]i, and induces activation of Na+/H+ exchange which raises the cytosolic pH, pHi. Recent studies have addressed the question whether Na+/H+ exchange plays a role in Ca2+ influx and, specifically, whether a rise in pHi 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 pHi 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 pHi and Ca2+ rises, measured with fluorescent indicators, suggests that the increase in [Ca2+]i distinctly precedes the increase in pHi. This challenges the concept that alkalinization per se is a sufficient signal for the opening of Ca2+ channels in the plasma membrane.
