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.


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 microm capsazepine showed no effect on bladder irritation by acetic acid. TRPA1 and TRPM8 did not show sex differences in their expression.


CONCLUSIONS
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.
Kobayashi
Hideki
H
Department of Urology, University of Yamanashi Interdisciplinary Graduate School of Medicine and Engineering, Chuo, Japan.
Yoshiyama
Mitsuharu
M
Zakoji
Hidenori
H
Takeda
Masayuki
M
Araki
Isao
I
D062565:Acid Sensing Ion Channels; D000818:Animals; D018856:Cystitis, Interstitial / Q000209:etiology*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012727:Sex Characteristics; D015222:Sodium Channels / Q000378:metabolism*; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism*
C568267:ASIC1 protein, mouse; C568265:ASIC2 protein, mouse; D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse