24 | Smooth muscle cells from human vagina express functional transient receptor potential channels

Francesco Palmieri¹, R. Garella¹, I. Cellai², G. Guarnieri¹, E. Maseroli², S. Cipirani², M. Annunziato², P. Comeglio², A. Morelli¹, M. Maggi², L. Vignozzi², R. Squecco¹ | ¹Dip. di Medicina Sperimentale e Clinica, Università di Firenze, Italy; ²Dip. di Scienze Biomediche Sperimentali e Cliniche, Università di Firenze, Italy.

Smooth muscle cells play a critical role in the physiology of the human vagina, especially in conditions such as the menopause, in which the decline of sex hormones levels can cause effects such as thinning of the epithelium and decreased muscle tone, impairing tissue elasticity and human vaginal smooth muscle cells (hvSMC) contractility. Elucidating the membrane proteins that regulate their activity is essential for the comprehension of the mechanisms underlying vaginal physiology and pathophysiology. Among these, Transient Receptor Potential (TRP) channels are transmembrane protein complexes acting as nonselective cation channels which can be modulated by sex hormones. They are widely expressed in several tissues, playing a pivotal role in processes as mechano-transduction, flogosis and thermal nociception. Although TRP channels have emerged as key modulators of calcium signaling and smooth muscle contractility, their effective role in hvSMCs remain largely unexplored. In this study we aimed to evaluate the expression and functionality of TRP channels in hvSMCs, considering that their activity could be disturbed following hormonal changes occurring in the menopause. We first evaluated the TRP channels expression in hvSMCs by RT-PCR and immunohistochemical analyses. The functionality of the channels was assessed by the wholecell patch clamp technique, using chemical and thermal stimuli for their activation. Our analyses showed a high expression of mRNA related to TRPV1 and TRPA1, whereas the expression of TRPM8 resulted significantly lower. The electrophysiological analyses showed that chemical and thermal stimuli were able to activate the three channels, causing an increase in current amplitude proportional to their expression. In conclusion, our results show for the first time that TRP channels are widely expressed and functional in isolated hvSMCs, and can represent a potential therapeutic target for the treatment of gynecological diseases.