InsP3-dependent Ca2+ oscillations linked to activation of voltage-dependent H+ conductance in Rana esculenta oocytes

In normal medium supplemented with 10 mM tetraethylammonium chloride (TEACl), membrane depolarizations of immature Rana esculenta oocytes elicited an oscillatory outward current associated with a voltage-dependent H+ current (IH+). The voltage threshold of these oscillations was 22 +/- 5 (n = 10). The oscillations were blocked by intracellular injection of ethylene glycol-O,O'-bis-(2-acetaminoethyl)-N,N,N',N'-tetraacetic acid (EGTA), by application of 1 mM of 4-acetamido-4'-isocyanatostilbene-2,2'-disulfonic acid (SITS), by caffeine (1 mM), and by the intracellular injection of heparin, suggesting that they arose from calcium release from inositol trisphosphate (InsP3)-sensitive stores, monitored by a calcium-dependent chloride current (IClCa2+). The oscillations were independent of the external calcium concentration, and the depolarizations did not affect the InsP3 level. Ni2+, a IH+ inhibitor, blocked the oscillations. Extracellular alkalinization, which lowered the voltage threshold of IH+ and increased its amplitude, also lowered the voltage threshold of the oscillations and increased their amplitude, whereas extracellular acidification produced opposite effects. We suggest that the oscillations are linked to activation of IH+ through a pH-dependent sensitization of InsP3 receptors.