Na+/H+ exchange and Ca2+ influx.
Cell stimulation raised the cytosolic free Ca2+ concentration, [Ca(2+]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 Ca(2+) influx and, specifically, whether a rise in pHi alone suffices to open Ca(2+) channels in the plasma membrane. Artificial cytosolic alkalinization can induce Ca(2+) uptake across the plasma membrane of endothelial cells, lymphocytes and smooth muscle cells. Furthermore, inhibition of Na+/H+ exchange reduces agonist-induced Ca(2+) influx in endothelial cells and platelets which supports the concept that pHi may regulate the opening of Ca(2+) channels in the plasma membrane. Although these findings argue in favour of a role of Na+/H+ exchange in Ca(2+) influx, the onset of pHi and Ca(2+) rises, measured with fluorescent indicators, suggests that the increase in [Ca(2+)]i distinctly precedes the increase in pHi. This challenges the concept that alkalinization per se is a sufficient signal for the opening of Ca(2+) channels in the plasma membrane.
Siffert
W
W
Max-Planck-Institut für Biphysik, FRG.
Akkerman
J W
JW
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D002468:Cell Physiological Phenomena; D004727:Endothelium / Q000502:physiology; D005057:Eukaryotic Cells / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D009130:Muscle, Smooth / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D002118:Calcium