Potentiation of 17β-estradiol on neuroexcitability by HCN-mediated neuromodulation of fast-afterhyperpolarization and late-afterdepolarization in low-threshold and sex-specific myelinated Ah-type baroreceptor neurons via GPR30 in female rats

Abstract

17β-Estradiol (17β-E2), as a female hormone, demonstrates a boarder role in modulating neuroexcitability of visceral afferent neurons [1], such as baroreceptor neurons (BRNs), hence, participating in the baroreflex function [2], the cellular and ion channel mechanisms involved in this function have always attracted the keen attention of investigators. A wealth of information indicates that 17β-E2 enhances the excitability in both CNS neurons [3] and visceral afferent neurons including BRNs [4] by modification of expression profiles of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels [5] underlying the funny current (If) or hyperpolarization-activated current (Ih), which is originally described in sinoatrial node myocytes as an inward current activated on hyperpolarization to the diastolic range of voltages and has the capability for generating repetitive activity [6].