Insulin facilitates the induction of the slow Na+ channels in immature Xenopus oocytes.
Endogenous slow sodium channels have been described in the membrane 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 enzymatic 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 receptor tyrosine kinases and to activate PLC-gamma 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 indicated 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.
Charpentier
G
G
Laboratoire de Physiologie Animale, Faculté des Sciences, Université de Picardie Jules Verne, Amiens Cedex, France. Gilles.Charpentier@nbcm.cnrs-gif.fr
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000008:administration & dosage*; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology*; D014982:Xenopus laevis
D007328:Insulin; D015222:Sodium Channels