Sex differences in the expression profile of acid-sensing ion channels in the mouse urinary bladder: a possible involvement in irritative bladder symptoms

OBJECTIVE To investigate the expressions and sex differences of acid-sensitive ion channels (i.e. ASIC and transient receptor potential channel V1, TRPV1; both key receptors for extracellular protons that might underlie the acid-evoked pain perception) and other nociceptive ion channels in the mouse bladder. MATERIALS AND METHODS Mucosa and muscle layers of the urinary bladder were separately taken from male and female mice. The gene expressions of ASIC subunits, TRPV1, TRPA1 and TRPM8 were quantified using real-time reverse transcriptase-polymerase chain reaction. The localization of ASIC protein was explored using immunohistochemistry. Continuous-filling cystometry was used to examine the effects of capsazepine, a TRPV1 blocker, on the bladder response to acetic acid. RESULTS ASIC1 was the dominant ASIC subunit expressed in bladder epithelium, whereas both ASIC1 and ASIC2 were expressed in bladder smooth muscle. ASIC3 expression was much less abundant, but localized in the subepithelial region. In the mucosa, the ASIC1 gene was more highly expressed in male than in female mice, whereas the expression level of ASIC2 in the bladder muscle was higher in female than in male mice. The expression of TRPV1 in the bladder showed a sex difference (male < female), but it was much lower than ASIC genes. Furthermore, the intravesical administration of 100 mu m capsazepine showed no effect on bladder irritation by acetic acid. TRPA1 and TRPM8 did not show sex differences in their expression. CONCLUSION The expression of ASIC subunit in the bladder was abundant and showed significant sex differences. Thus, ASICs might be involved in the sex difference in the bladder response to acidic irritation.