Melanocortin type 4 receptor-mediated inhibition of A-type K⁺ current enhances sensory neuronal excitability and mechanical pain sensitivity in rats.

ABSTRACT: α-Melanocyte-stimulating hormone (α-MSH) has been shown to be involved in nociception, but the underlying molecular mechanisms remain largely unknown. In this study, we report that α-MSH suppresses the transient outward A-type K⁺ current (I _A) in trigeminal ganglion (TG) neurons and thereby modulates neuronal excitability and peripheral pain sensitivity in rats. Exposing small-diameter TG neurons to α-MSH concentration-dependently decreased I _A This α-MSH-induced I _A decrease was dependent on the melanocortin type 4 receptor (MC4R) and associated with a hyperpolarizing shift in the voltage dependence of A-type K⁺ channel inactivation. Chemical inhibition of phosphatidylinositol 3-kinase (PI3K) with wortmannin or of

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6462507 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature