Enhancement of T-type Ca2+ channel currents in dorsal root ganglia neurons by nesfatin-1 and possible mechanisms

Abstract

Objective To investigate the effect of nesfatin-1(NSF-1) on T-type Ca2+ channel currents in adult mouse dorsal root ganglion(DRG) neurons and possible signal transduction mechanisms involved. Methods We measured the expression of melanocortin 4 receptors(MC4-R) in mouse DRG by using western blotting analysis. The whole-cell patch clamp technique was used to record the effects of NSF-1 on T-type Ca2+ channel currents in small DRG neurons and several ligands were experimented to further clarify relevant signaling pathways. Results MC4-Rs were abundantly expressed in DRG neurons. NSF-1 enhanced T-type calcium channel currents in a dose-dependent manner in small DRG neurons in mice. NSF-1-mediated increment of T-type calcium channel currents was blocked by the MC4-R antagonist HS024, phosphokinase C antagonists GF109203X, and chelerythrine chloride, while the blockade of phospohokinase A PKI 6-22 elicited no such effects. Conclusions NSF-1 can enhance T-type calcium channel currents in small DRG neurons through an MC4-R-dependent PKC signaling pathway. Key words: Melanocortins; Calcium channels, T-type; Ganglia, spinal