AQP2 can modulate the pattern of Ca 2+ transients induced by store-operated Ca 2+ entry under TRPV4 activation

RIVAROLA, VALERIA; PIZZONI, ALEJANDRO; RIVAROLA, VALERIA; PIZZONI, ALEJANDRO; FORD, PAULA; DI GIUSTO, GISELA; FORD, PAULA; DI GIUSTO, GISELA; CAPURRO, CLAUDIA; LÓPEZ GONZÁLEZ, MACARENA; CAPURRO, CLAUDIA; LÓPEZ GONZÁLEZ, MACARENA

JOURNAL OF CELLULAR BIOCHEMISTRY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2017 p. 4120 - 4133

0730-2312

There is increasingevidence indicating that aquaporins (AQPs) exert an influence in cell signalingby the interplay with the TRPV4 Ca2+ channel. Ca2+release from intracellular storesand plasma membrane hyperpolarization due to opening of Ca2+-activated potassiumchannels (KCa) are events that have been proposed to take place downstream of TRPV4activation. A major mechanism for Ca2+ entry, activated after depletion of intracellularCa2+stores and driven by electrochemical forces, is the store-operated Ca2+ entry(SOCE). The consequences of the interplay between TRPV4 and AQPs on SOCE have notbeen yet investigated. The aim of our study was to test the hypothesis that AQP2can modulate SOCE by facilitating the interaction of TRPV4 with KCa channels inrenal cells. Using fluorescent probe techniques, we studied intracellular Ca2+concentrationand membrane potential in response to activation of TRPV4 in two rat cortical collectingduct cell lines (RCCD1), one not expressing AQPs (WT-RCCD1) and the other transfectedwithAQP2 (AQP2-RCCD1).We found that AQP2 co-immunoprecipitates with TRPV4 and with the small-conductancepotassium channel (SK3). We also showed that AQP2 is crucial for the activationof SK3 by TRPV4, leading to hyperpolarization of the plasma membrane. This seemsto be relevant to modulate the magnitude of SOCE and is accompanied by TRPV4 translocationto the plasma membrane only in AQP2 expressing cells. These findings open the perspectiveto further investigate whether the interplay between different AQPs with TRPV4 andKCa channels can be an important mechanism to modulate SOCE with physiological relevance