Castration Induces Down-Regulation of A-Type K+ Channel in Rat Vas Deferens Smooth Muscle

Susumu Ohya,Akitoshi Ohno,Yuji Imaizumi,Katsunori Ito,Noriyuki Hatano,Katsuhiko Muraki

doi:10.3390/ijms20174073

Abstract

A-type K+ channels contribute to regulating the propagation and frequency of action potentials in smooth muscle cells (SMCs). The present study (i) identified the molecular components of A-type K+ channels in rat vas deferens SMs (VDSMs) and (ii) showed the long-term, genomic effects of testosterone on their expression in VDSMs. Transcripts of the A-type K+ channel α subunit, Kv4.3L and its regulatory β subunits, KChIP3, NCS1, and DPP6-S were predominantly expressed in rat VDSMs over the other related subtypes (Kv4.2, KChIP1, KChIP2, KChIP4, and DPP10). A-type K+ current (IA) density in VDSM cells (VDSMCs) was decreased by castration without changes in IA kinetics, and decreased IA density was compensated for by an oral treatment with 17α-methyltestosterone (MET). Correspondingly, in the VDSMs of castrated rats, Kv4.3L and KChIP3 were down-regulated at both the transcript and protein expression levels. Changes in Kv4.3L and KChIP3 expression levels were compensated for by the treatment with MET. These results suggest that testosterone level changes in testosterone disorders and growth processes control the functional expression of A-type K+ channels in VDSMCs.

Highlights

Testosterone, the male sex hormone is responsible for the virilization of the Wolffian duct system into the epididymis, vas deferens, and seminal vesicle [1]
neuronal Ca2+ sensor 1 (NCS1) does not affect the voltage dependence of inactivation or the rate of recovery from the inactivation of Kv4 channels [30]. These findings suggest that DPP6-S but not KChIP3 or NCS1 strongly contributes to the modification of Kv4.3L channel kinetics in rat vas deferens (VD) smooth muscle cells (VDSMCs)
Ca2+-dependent interactions between KChIP3 and cAMP response element binding (CREB) have been shown to represent a point of cross-talk between cAMP and Ca2+ signaling pathways in the nucleus [34]. These findings suggest that the gene expression of Kv4.3 or KChIP3 is associated with the signaling pathway mediating some growth factors, mitogen-activated protein kinase (MAPK), or CREB protein transcription factors in vas deferens SMs (VDSMs)

Summary

Introduction

Testosterone, the male sex hormone is responsible for the virilization of the Wolffian duct system into the epididymis, vas deferens, and seminal vesicle [1]. The testosterone-mediated development of the Wolffian duct is regulated by a number of growth factors, including epidermal growth factor (EGF), insulin-like growth factor (IGF), and fibroblast growth factor (FGF) [2]. Castration significantly decreases serum testosterone levels, and this is accompanied by significant reductions in the weight of the vas deferens (VD) [3]. Boselli et al (1994) indicated that castration decreased K+ conductance in VD smooth muscle cells (VDSMCs) [6]. VDSMCs functionally express rapidly-inactivating, voltage-dependent (A-type) K+ channels [7]. The long-term, genomic effects of testosterone on the gene expression of A-type K+ channel subunits remain to be elucidated in VDSMs

Methods

Results

Discussion

Conclusion