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lüll Modulation of TRPV4 gating by intra- and extracellular Ca2+ Watanabe H; Vriens J; Janssens A; Wondergem R; Droogmans G; Nilius BCell Calcium 2003[May]; 33 (5-6): 489-95We have studied the modulation of gating properties of the Ca2+-permeable, cation channel TRPV4 transiently expressed in HEK293 cells. The phorbol ester 4alphaPDD transiently activated a current through TRPV4 in the presence of extracellular Ca2+. Increasing the concentration of extracellular Ca2+ ([Ca2+](e)) reduced the current amplitude and accelerated its decay. This decay was dramatically delayed in the absence of [Ca2+](e). It was also much slower in the presence of [Ca2+](e) in a mutant channel, obtained by a point mutation in the 6th transmembrane domain, F707A. Mutant channels, containing a single mutation in the C-terminus of TRPV4 (E797), were constitutively open. In conclusion, gating of the 4alphaPDD-activated TRPV4 channel depends on both extra- and intracellular Ca2+, and is modulated by mutations of single amino acid residues in the 6th transmembrane domain and the C-terminus of the TRPV4 protein.|Amino Acid Substitution[MESH]|Cation Transport Proteins/drug effects/*physiology[MESH]|Cations/*metabolism[MESH]|Cells, Cultured[MESH]|Electrophysiology[MESH]|Extracellular Space[MESH]|Humans[MESH]|Intercellular Junctions[MESH]|Ion Channel Gating/*physiology[MESH]|Ion Channels/drug effects/*physiology[MESH]|Mutation[MESH]|Phorbols/*pharmacology[MESH]|TRPV Cation Channels[MESH] |