Insulin Facilitates the Induction of the Slow Na+ Channels in Immature Oocytes

Abstract. Endogenous slow sodium channels have been described in the mem-brane of immature Xenopus laevis oocytes. The opening of these channels is a complex process comprising an induction phase leading the channels from a state of electrical inexcitability into a voltage-dependent state. The mechanism by which the depolarization of the membrane causes the induction is dependent upon an en-zymatic cascade implying a phospholipase C (PLC) and a protein kinase C (PKC). The existence of different isoforms of PLC has been described in the oocytes, each isoform being activated by distinct membrane receptors upon ligand binding. The present work investigated the effects of insulin known to bind to membrane recep-tor tyrosine kinases and to activate PLC-γ isoforms. Our results in current and voltage clamp experiments showed that insulin facilitated the induction of the slow Na+ channels in a dose-dependent way. The current/voltage relationships indi-cated that the gating properties of the channels were not altered by the hormone. Lavendustins and tyrphostin, inhibitors of the epidermal growth factor signaling pathway, failed to block insulin effect as well as induction of the sodium channels. The results support the idea that some of the enzymes activated by insulin could also be involved in the acquisition of the channel voltage dependency and activated by sustained depolarization of the membrane