title: Hysteresis of gating underlines sensitization of TRPV3 channels.
abstract: Vanilloid receptors of the transient receptor potential family have functions in thermal sensation and nociception. Among them, transient receptor potential vanilloid (TRPV)3 displays a unique property by which the repeated stimulation causes successive increases in its activity. The property has been known as sensitization and is observed in both native cells and cells heterologously expressing TRPV3. Transient increases in intracellular calcium levels have been implicated to play a key role in this process by mediating interaction of calmodulin with the channel. In support of the mechanism, BAPTA, a fast calcium chelator, accelerates the sensitization, whereas the slow chelator EGTA is ineffectual. Here, we show that the sensitization of TRPV3 also occurred independently of Ca(2+). It was observed in both inside-out and outside-out membrane patches. BAPTA, but not EGTA, has a direct potentiation effect on channel activation. Analogues of BAPTA lacking Ca(2+)-buffering capability were similarly effective. The stimulation-induced sensitization and the potentiation by BAPTA are distinguishable in reversibility. We conclude that the sensitization of TRPV3 is intrinsic to the channel itself and occurs as a result of hysteresis of channel gating. BAPTA accelerates the sensitization process by potentiating the gating of the channel.
authors: Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
authors: Beiying
authors: B
authors: Liu
authors: Jing
authors: J
authors: Yao
authors: Michael X
authors: MX
authors: Zhu
authors: Feng
authors: F
authors: Qin
mesh_terms: D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D015394:Molecular Structure; D018408:Patch-Clamp Techniques; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D050916:TRPV Cation Channels; C459445:TRPV3 protein, human; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium