Increased expression of TRPC4 channels associated with erectile dysfunction in diabetes.

Abstract

In recent reports, an association between altered TRPC channel function and the

development of various diabetic complications has drawn the attention of many

investigators. The aim of this study was to investigate the expression of TRPC4

channels of corpus smooth muscle (CSM) cells in diabetes, and to evaluate the

association between erectile dysfunction (ED) and altered TRPC4 channel function.

The expression of TRPC4 in the penile tissue of human, normal and diabetic rat

was investigated using RT-PCR, western blotting and immunohistochemistry (IHC).

In vivo gene transfer of dominant negative (DN) TRPC4 into the CSM of rat was

conducted. In vivo pelvic nerve stimulation was performed to measure erectile

function. Expression of TRPC1, TRPC3, TRPC4 and TRPC6 in human and rat CSM

tissues was confirmed by RT-PCR, western blot and IHC. In the diabetic rat, the

expression levels of mRNA and protein of the TRPC4, and TRPC6 were significantly

increased compared to control rats (p < 0.05). The change in TRPC4 expression in

the diabetic rats was higher than those of the other TRPC subunits (p < 0.05).

The IHC showed that only TRPC4 expression had a higher intensity in the diabetes

compared to normal rats (p < 0.05). Gene transfection with TRPC4(DN) into the

diabetic rats restored erectile function to levels similar to that of normal

controls. Gene expression of TRPC4(DN) in CSM tissue was confirmed by RT-PCR 2

weeks after transfection. This study demonstrated that TRPC4 channel expression

increased in the penile CSM cells of diabetic rats. The down-regulation of TRPC4

with DN form restored erectile function in the diabetic rats. The alteration of

TRPC4 channel is one of pathophysiology of ED and could be a target for drug

development for ED.