Activation of TRPV4 promotes transepithelial K+ secretion in rat vaginal epithelium.

BACKGROUND

Transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel that regulates diverse biological processes, including osmoregulation, thermosensation, and ion transport. As a key component of the female reproductive tract, the vaginal epithelium plays a crucial role in maintaining luminal moisture and lubrication. However, the contribution of TRPV4 to vaginal epithelial function remains unclear.

AIM: To characterize the expression pattern of TRPV4 in vaginal epithelial cells and to elucidate its physiological role in regulating transepithelial ion transport and vaginal lubrication.

METHODS

Female SD rats were used in this study. Primary culture of rat vaginal epithelial cells was established. TRPV4 expression levels, transepithelial ion transport, and vaginal fluid secretion were measured.

OUTCOMES: The primary outcome of the study was the functional relationship between TRPV4 activation and vaginal lubrication.

RESULTS

TRPV4 was expressed in rat vaginal epithelial cells and that its activation promoted transepithelial K+ secretion across vaginal epithelium. Pharmacological blockade of large-conductance Ca2+-activated K+ channel (BKCa) but not ATP-sensitive K+ channel significantly attenuated TRPV4-mediated transepithelial K+ secretion, indicating functional coupling between TRPV4 and BKCa. In vivo studies revealed that activation of TRPV4 robustly enhanced vaginal fluid secretion in rats.

CLINICAL IMPLICATIONS: TRPV4-BKCa axis represents a potential molecular target for the treatment of female reproductive disorders characterized by vaginal dryness and impaired lubrication.

STRENGTHS AND LIMITATIONS: The combined in vitro and in vivo approaches provide mechanistic insight into TRPV4-mediated regulation of vaginal fluid secretion. However, the absence of human tissues or clinical data limits the direct translational extrapolation of these findings.

CONCLUSION

This study identifies TRPV4 as a key regulator of vaginal moistness and lubrication, providing novel insights into the physiological mechanisms governing female reproductive function and suggesting new therapeutic avenues for conditions associated with vaginal dryness.