Inositol trisphosphate may access calcium from stores not coupled to muscarinic receptors in Xenopus oocytes

Oocytes of a large fraction of Xenopus females exhibit a complex response to acetylcholine (ACh) consisting of rapid, transient and prolonged, slow chloride currents. Frequent consecutive challenges or a single prolonged challenge with ACh result in a marked decrease in response amplitudes, i. e. refractoriness. In ACh-refractory oocytes, the response to injected inositol 1,4,5,-trisphosphate (Ins P₃,), the intracellular mediator of the ACh response, is not affected. Similarly, Ins P₃-evoked responses were obtained in oocytes that lacked muscarinic response or that lost their responsiveness as a result of progesterone-induced maturation. To investigate the mechanism of this phenomenon, we have depleted intracellular calcium stores by repeated challenges with ACh in calcium-free medium. Disappearance of the ACh response through depletion of the ACh-coupled calcium store did not prevent a subsequent response to Ins P₃. These results imply that Ins P₃ can mobilize calcium from other stores, not depleted by previous exposure to ACh. This finding is further reinforced by our results that demonstrate that ACh causes ⁴⁵Ca efflux in responsive oocytes, while Ins P₃ in supramaximal concentrations does not induce ⁴⁵Ca efflux. Indeed, Ins P₃ can induce ⁴⁵Ca efflux only when more than 2 pmol/oocyte is injected. This is also the concentration of Ins P₃ that desensitizes the Ins P₃ response. These data suggest that Ins P₃ also releases cellular calcium from stores different from those mobilized by ACh.