The speed of swelling kinetics modulates cell volume regulation and calcium signaling in astrocytes: A different point of view on the role of aquaporins

Maria Grazia Mola, Angelo Sparaneo, Concetta Domenica Gargano, David C. Spray, Maria Svelto, Antonio Frigeri, Eliana Scemes, Grazia Paola Nicchia

Research output: Contribution to journalArticle

Abstract

Regulatory volume decrease (RVD) is a process by which cells restore their original volume in response to swelling. In this study, we have focused on the role played by two different Aquaporins (AQPs), Aquaporin-4 (AQP4), and Aquaporin-1 (AQP1), in triggering RVD and in mediating calcium signaling in astrocytes under hypotonic stimulus. Using biophysical techniques to measure water flux through the plasma membrane of wild-type (WT) and AQP4 knockout (KO) astrocytes and of an astrocyte cell line (DI TNC1) transfected with AQP4 or AQP1, we here show that AQP-mediated fast swelling kinetics play a key role in triggering and accelerating RVD. Using calcium imaging, we show that AQP-mediated fast swelling kinetics also significantly increases the amplitude of calcium transients inhibited by Gadolinium and Ruthenium Red, two inhibitors of the transient receptor potential vanilloid 4 (TRPV4) channels, and prevented by removing extracellular calcium. Finally, inhibition of TRPV4 or removal of extracellular calcium does not affect RVD. All together our study provides evidence that (1) AQP influenced swelling kinetics is the main trigger for RVD and in mediating calcium signaling after hypotonic stimulus together with TRPV4, and (2) calcium influx from the extracellular space and/or TRPV4 are not essential for RVD to occur in astrocytes. GLIA 2016;64:139-154 Main Points: The speed of swelling kinetics is the main trigger for Regulatory Volume Decrease (RVD) and for calcium response in astrocytes. Calcium influx from the extracellular space and TRPV4 are not essential for RVD.

Original languageEnglish
Pages (from-to)139-154
Number of pages16
JournalGLIA
Volume64
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • AQP1
  • AQP4
  • Cell swelling
  • Hypotonic stimulus
  • RVD

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Fingerprint Dive into the research topics of 'The speed of swelling kinetics modulates cell volume regulation and calcium signaling in astrocytes: A different point of view on the role of aquaporins'. Together they form a unique fingerprint.

  • Cite this