Injection of inositol 1, 3, 4, 5-tetrakisphosphate into Xenopus oocytes generates a chloride current dependent upon intracellular calcium

Abstract

Injection of inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P$_{4}$) into voltage-clamped oocytes of Xenopus laevis elicited an oscillatory chloride membrane current. This response did not depend upon extracellular calcium, because it could be produced in calcium-free solution and after addition of cobalt to block calcium channels in the surface membrane. However, it was abolished after intracellular loading with the calcium chelating agent EGTA, indicating a dependence upon intracellular calcium. The mean dose of (Ins(1,3,4,5)P$_{4}$) required to elicit a threshold current was 4 $\times $ 10$^{-14}$ mol. In comparison, inositol 1,4,5-trisphosphate (Ins(1,4,5)P$_{3}$) gave a similar oscillatory current with doses of about one twentieth as big. Hyperpolarization of the oocyte membrane during activation by Ins(1,3,4,5)P$_{4}$ elicited a transient inward current, as a result of the opening of calcium-dependent chloride channels subsequent to the entry of external calcium. In some oocytes the injection of (Ins(1,3,4,5)P$_{4}$) was itself sufficient to allow the generation of the transient inward current, whereas in others a prior injection of Ins(1,4,5)P$_{3}$ was required. We conclude that Ins(1,3,4,5)P$_{4}$ causes the release of intracellular calcium from stores in the oocyte, albeit with less potency than Ins(1,4,5)P$_{3}$. In addition, Ins(1,3,4,5)P$_{4}$ activates voltage-sensitive calcium channels in the surface membrane, via a process that may require `priming' by Ins(1,4,5)P$_{3}$.