TRPV4 was identified as the mammalian homologue of the C. elegans osmosensory channel protein, OSM-9. This nonselective cation channel is activated in vitro by even modest degrees of hypotonic cell swelling. Its expression in the mammalian central nervous system and kidney suggests a role in systemic osmoregulation-a view borne out by detailed balance studies in TRPV4-null mice. Two distinct mechanisms have been described through which TRPV4 may be activated by hypotonicity: one involves the SRC family of nonreceptor protein tyrosine kinases, while the other is mediated via arachidonic acid metabolites.
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