info:eu-repo/semantics/article
TRPV4 Contributes to Resting Membrane Potential in Retinal Müller Cells: Implications in Cell Volume Regulation
Fecha
2017-08Registro en:
Netti, Vanina Alejandra; Fernández, Juan; Kalstein, Maia; Pizzoni, Alejandro; Di Giusto, Gisela; et al.; TRPV4 Contributes to Resting Membrane Potential in Retinal Müller Cells: Implications in Cell Volume Regulation; Wiley-liss, Div John Wiley & Sons Inc; Journal of Cellular Biochemistry; 118; 8; 8-2017; 2302-2313
0730-2312
CONICET Digital
CONICET
Autor
Netti, Vanina Alejandra
Fernández, Juan
Kalstein, Maia
Pizzoni, Alejandro
Di Giusto, Gisela
Rivarola, Valeria
Ford, Paula
Capurro, Claudia Graciela
Resumen
Neural activity alters osmotic gradients favoring cell swelling in retinal Müller cells. This swelling is followed by a regulatory volume decrease (RVD), partially mediated by an efflux of KCl and water. The transient receptor potential channel 4 (TRPV4), a nonselective calcium channel, has been proposed as a candidate for mediating intracellular Ca2+ elevation induced by swelling. We previously demonstrated in a human Müller cell line (MIO-M1) that RVD strongly depends on ion channel activation and, consequently, on membrane potential (Vm ). The aim of this study was to investigate if Ca2+ influx via TRPV4 contributes to RVD by modifying intracellular Ca2+ concentration and/or modulating Vm in MIO-M1 cells. Cell volume, intracellular Ca2+ levels, and Vm changes were evaluated using fluorescent probes. Results showed that MIO-M1 cells express functional TRPV4 which determines the resting Vmassociated with K+ channels. Swelling-induced increases in Ca2+ levels was due to both Ca2+ release from intracellular stores and Ca2+ influx by a pathway alternative to TRPV4. TRPV4 blockage affected swelling-induced biphasic response (depolarization-repolarization), suggesting its participation in modulating Vm changes during RVD. Agonist stimulation of Ca2+ influx via TRPV4 activated K+ channels hyperpolarizing Vm and accelerating RVD. We propose that TRPV4 forms a signaling complex with Ca2+ and/or voltage-dependent K+ channels to define resting Vm and Vm changes during RVD. TRPV4 involvement in RVD depends on the type of stimuli and/or degree of channel activation, leading to a maximum RVD response when Ca2+ influx overcomes a threshold and activates further signaling pathways in cell volume regulation.