Neural Growth Factor Increases the Cationic Non-Selective Currents in Neonatal Rat Pancreatic Beta-Cells

Neural growth factor (NGF) is secreted by pancreatic beta-cells, which also present NGF auto-receptors with high (TrkA) and low (p75) affinities. NGF promotes beta cell survival and enhances glucose-stimulated insulin-secretion. The latter has been associated to an increase in the number of voltage-gated Na+ and Ca2+ channels at the plasma membrane. However, further research is necessary to understand if other ion channels are implicated in NGF signaling.In the present study, the long-term effect of NGF on the cationic non-selective (CAN) currents of beta cells from neonate rats was characterized, and compared to that of mature animals.Pancreatic islets from adult and neonatal male Wistar rats were isolated and separated from acinar tissue by collagenase digestion and a density Ficoll gradient. Isolated cells were obtained from islets after an enzymatic digestion with trypsin. Whole-cell patch clamp recordings were obtained from beta cells with membrane capacitances of 6.0 ± 0.2 pF (N=32) and 6.3 ± 0.3 pF (N=28), for neonatal and adult rats, respectively.Control adult beta cells showed a higher CAN density current compared to control neonatal cells. When the latter were incubated with NGF (50 ng/ml) during 48 h, CAN currents significantly increased in more than 2-fold at two test potentials, −120 and 80 mV, reaching a similar level to adult cells. Moreover, the effect of NGF was reverted by the incubation with K252a (200 nM), a blocker of high affinity TrkA receptors. Taken together, our results suggest that NGF could contribute to beta cell maturation by a gain of function in CAN currents.Partially supported by Consejo Nacional de Ciencia y Tecnologia CONACYT CB2009-131647, and DGAPA-PAPIIT IN215611, Universidad Nacional Autonoma de Mexico. Carlos Manlio Diaz-Garcia has a fellowship from CONACyT.