Role of the wáter cannel AQP4 in retinal Muller cells homeostasis

JUAN FERNADEZ; MAIA KALSTEIN; V . RIVAROLA; G. DI GIUSTO; P. FORD; C . CAPURRO

FOZ DE IGUAZU

Congreso; 1st PanAmerican Congress of Physiological Science; 2014

ROLE OF THE WATER CHANNEL AQP4 IN RETINAL MULLER CELL VOLUME HOMEOSTASIS Juan Fernandez; Maia Kalstein; Gisela Di Giusto; Valeria Rivarola; Paula Ford; Claudia Capurro Dpto. Cs. Fisiologicas, Facultad Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. Müller cells are involved in controlling extracellular homeostasis in the retina, where neural activity alters osmotic gradients favoring cell swelling. This swelling is followed by a regulatory volume decrease (RVD), partially mediated by an iso-osmotic flux of KCl through ion channels and Aquaporin 4 (AQP4), a water channel identified as the antigen implicated in the pathogenesis of a central nervous system disease, Neuromyelitis Optica (NMO). We have recently shown in a retinal Müller cell line (MIO-M1) that RVD is strongly modulated by concurrent changes in the membrane potential (Vm). The aim of this study was to identify the signaling pathway involved in RVD response focusing in the participation of a mecanosensitive Ca2+ channel, TRPV4 supposed to be associated with AQP4, as well as the consequences of the exposition to IgG-NMO. Cell volume, intracellular Ca2+ and Vm changes were evaluated using fluorescent probes. Results showed a functional interaction between TRPV4 and Ca2+-sensitive K+ channels to define the steady-state Vm. Cell swelling induces Ca2+ increase independently of TRPV4 activity although this channel participates of the Vm changes occurring during RVD. Exposition to IgG-NMO sera reduces AQP4 expression and RVD response without affecting either TRPV4 expression or its function. These results demonstrate that Müller cell volume homeostasis requires functional AQP4 and TRPV4 both contributing by different pathways to the RVD response.