Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
Department of Molecular and Cellular Pharmacology, Graduate School of Pharmacological Sciences, Nagoya City University, Nagoya 467-8603, Japan.
Int J Mol Sci. 2019 Aug 21;20(17):4073. doi: 10.3390/ijms20174073.
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 (I) density in VDSM cells (VDSMCs) was decreased by castration without changes in I kinetics, and decreased I 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.
A 型钾通道有助于调节平滑肌细胞（SMCs）中动作电位的传播和频率。本研究（i）鉴定了大鼠输精管平滑肌（VDSMs）中 A 型钾通道的分子成分，（ii）显示了睾酮对其在 VDSMs 中表达的长期、基因组效应。A 型钾通道 α 亚基、Kv4.3L 及其调节 β 亚基 KChIP3、NCS1 和 DPP6-S 的转录本在大鼠 VDSMs 中的表达明显高于其他相关亚型（Kv4.2、KChIP1、KChIP2、KChIP4 和 DPP10）。去势不会改变 I 动力学，但会降低 VDSM 细胞（VDSMCs）中 A 型钾电流（I）密度，而口服 17α-甲基睾酮（MET）治疗可补偿降低的 I 密度。相应地，在去势大鼠的 VDSMs 中，Kv4.3L 和 KChIP3 的转录本和蛋白表达水平均下调。Kv4.3L 和 KChIP3 表达水平的变化可通过 MET 治疗得到补偿。这些结果表明，睾酮水平变化在睾酮紊乱和生长过程中控制了 VDSMCs 中 A 型钾通道的功能表达。
