Ghrelin and Leptin increase voltage-gated Na+ and Ca2+ currents in the RIN-m5f insulin-producing cell line

Abstract

β-pancreatic islet cells generate action potentials (AP) spontaneously or in response to different stimuli. This is orchestrated by the activity of diverse voltage-gated ion channels in the plasma membrane. Therefore, metabolic signals that modify the functional expression of these channels may alter β-cells excitability and in consequence the secretion of insulin. In particular, two hormones that regulate the voluntary food intake, Ghrelin and Leptin, may affect glucose serum concentrations by altering plasma insulin release. In this work, we use the insulin-producing RIN-M5f cell line to study the effects of the chronic treatment with Ghrelin or Leptin on the functional expression of voltage-gated Na+ and Ca2+ channels. Cells were kept in culture and then subjected to patch-clamp electrophysiology. Our results show that chronic incubation with Ghrelin or Leptin (10 nM, 72 h) increased the frequency of the spontaneous APs and the macroscopic current density through Na+ and Ca2+ channels. The analysis of the components of the Ca2+ currents showed that Ghrelin and Leptin differentially increased low- and high-threshold channels without causing apparent changes in current kinetics. The study of the electrophysiological mechanisms in insulin-secreting cells associated with the effects of Ghrelin and Leptin may shed light on the molecular processes involved in the endocrine/metabolic balance.