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Expression and functional characterization of transient receptor potential vanilloid-related channel 4 (TRPV4) in rat cortical astrocytes.
Neuroscience. 2007 Sep 21; 148(4):876-92.N

Abstract

Cell-cell communication in astroglial syncytia is mediated by intracellular Ca(2+) ([Ca(2+)](i)) responses elicited by extracellular signaling molecules as well as by diverse physical and chemical stimuli. Despite the evidence that astrocytic swelling promotes [Ca(2+)](i) elevation through Ca(2+) influx, the molecular identity of the channel protein underlying this response is still elusive. Here we report that primary cultured cortical astrocytes express the transient receptor potential vanilloid-related channel 4 (TRPV 4), a Ca(2+)-permeable cation channel gated by a variety of stimuli, including cell swelling. Immunoblot and confocal microscopy analyses confirmed the presence of the channel protein and its localization in the plasma membrane. TRPV4 was functional because the selective TRPV4 agonist 4-alpha-phorbol 12,13-didecanoate (4alphaPDD) activated an outwardly rectifying cation current with biophysical and pharmacological properties that overlapped those of recombinant human TRPV4 expressed in COS cells. Moreover, 4alphaPDD and hypotonic challenge promoted [Ca(2+)](i) elevation mediated by influx of extracellular Ca(2+). This effect was abolished by low micromolar concentration of the TRPV4 inhibitor Ruthenium Red. Immunofluorescence and immunogold electron microscopy of rat brain revealed that TRPV4 was enriched in astrocytic processes of the superficial layers of the neocortex and in astrocyte end feet facing pia and blood vessels. Collectively, these data indicate that cultured cortical astroglia express functional TRPV4 channels. They also demonstrate that TRPV4 is particularly abundant in astrocytic membranes at the interface between brain and extracerebral liquid spaces. Consistent with its roles in other tissues, these results support the view that TRPV4 might participate in astroglial osmosensation and thus play a key role in brain volume homeostasis.

Authors+Show Affiliations

Department of Human and General Physiology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17719182

Citation

Benfenati, V, et al. "Expression and Functional Characterization of Transient Receptor Potential Vanilloid-related Channel 4 (TRPV4) in Rat Cortical Astrocytes." Neuroscience, vol. 148, no. 4, 2007, pp. 876-92.
Benfenati V, Amiry-Moghaddam M, Caprini M, et al. Expression and functional characterization of transient receptor potential vanilloid-related channel 4 (TRPV4) in rat cortical astrocytes. Neuroscience. 2007;148(4):876-92.
Benfenati, V., Amiry-Moghaddam, M., Caprini, M., Mylonakou, M. N., Rapisarda, C., Ottersen, O. P., & Ferroni, S. (2007). Expression and functional characterization of transient receptor potential vanilloid-related channel 4 (TRPV4) in rat cortical astrocytes. Neuroscience, 148(4), 876-92.
Benfenati V, et al. Expression and Functional Characterization of Transient Receptor Potential Vanilloid-related Channel 4 (TRPV4) in Rat Cortical Astrocytes. Neuroscience. 2007 Sep 21;148(4):876-92. PubMed PMID: 17719182.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression and functional characterization of transient receptor potential vanilloid-related channel 4 (TRPV4) in rat cortical astrocytes. AU - Benfenati,V, AU - Amiry-Moghaddam,M, AU - Caprini,M, AU - Mylonakou,M N, AU - Rapisarda,C, AU - Ottersen,O P, AU - Ferroni,S, Y1 - 2007/07/17/ PY - 2007/01/17/received PY - 2007/06/20/revised PY - 2007/07/19/accepted PY - 2007/8/28/pubmed PY - 2008/2/15/medline PY - 2007/8/28/entrez SP - 876 EP - 92 JF - Neuroscience JO - Neuroscience VL - 148 IS - 4 N2 - Cell-cell communication in astroglial syncytia is mediated by intracellular Ca(2+) ([Ca(2+)](i)) responses elicited by extracellular signaling molecules as well as by diverse physical and chemical stimuli. Despite the evidence that astrocytic swelling promotes [Ca(2+)](i) elevation through Ca(2+) influx, the molecular identity of the channel protein underlying this response is still elusive. Here we report that primary cultured cortical astrocytes express the transient receptor potential vanilloid-related channel 4 (TRPV 4), a Ca(2+)-permeable cation channel gated by a variety of stimuli, including cell swelling. Immunoblot and confocal microscopy analyses confirmed the presence of the channel protein and its localization in the plasma membrane. TRPV4 was functional because the selective TRPV4 agonist 4-alpha-phorbol 12,13-didecanoate (4alphaPDD) activated an outwardly rectifying cation current with biophysical and pharmacological properties that overlapped those of recombinant human TRPV4 expressed in COS cells. Moreover, 4alphaPDD and hypotonic challenge promoted [Ca(2+)](i) elevation mediated by influx of extracellular Ca(2+). This effect was abolished by low micromolar concentration of the TRPV4 inhibitor Ruthenium Red. Immunofluorescence and immunogold electron microscopy of rat brain revealed that TRPV4 was enriched in astrocytic processes of the superficial layers of the neocortex and in astrocyte end feet facing pia and blood vessels. Collectively, these data indicate that cultured cortical astroglia express functional TRPV4 channels. They also demonstrate that TRPV4 is particularly abundant in astrocytic membranes at the interface between brain and extracerebral liquid spaces. Consistent with its roles in other tissues, these results support the view that TRPV4 might participate in astroglial osmosensation and thus play a key role in brain volume homeostasis. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/17719182/Expression_and_functional_characterization_of_transient_receptor_potential_vanilloid_related_channel_4__TRPV4__in_rat_cortical_astrocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(07)00794-4 DB - PRIME DP - Unbound Medicine ER -