title: CaT1 and the calcium release-activated calcium channel manifest distinct pore properties.
abstract: The calcium release-activated calcium channel (CRAC) is a highly Ca(2+)-selective ion channel that is activated on depletion of inositol triphosphate (IP(3))-sensitive intracellular Ca(2+) stores. It was recently reported that CaT1, a member of the TRP family of cation channels, exhibits the unique biophysical properties of CRAC, which led to the conclusion that CaT1 comprises all or part of the CRAC pore (Yue, L., Peng, J. B., Hediger, M. A., and Clapham, D. E. (2001) Nature 410, 705-709). Here, we directly compare endogenous CRAC with heterologously expressed CaT1 and show that they manifest several clearly distinct properties. CaT1 can be distinguished from CRAC in the following features: sensitivity to store-depleting agents; inward rectification in the absence of divalent cations; relative permeability to Na(+) and Cs(+); effect of 2-aminoethoxydiphenyl borate (2-APB). Moreover, CaT1 displays a mode of voltage-dependent gating that is fully absent in CRAC and originates from the voltage-dependent binding/unbinding of Mg(2+) inside the channel pore. Our results imply that the pores of CaT1 and CRAC are not identical and indicate that CaT1 is a Mg(2+)-gated channel not directly related to CRAC.
authors.affiliation: Laboratory of Physiology, Catholic University of Leuven, B-3000 Leuven, Belgium. Thomas.Voets@kuleuven.ac.be
authors.forename: T
authors.initials: T
authors.lastname: Voets
authors.forename: J
authors.initials: J
authors.lastname: Prenen
authors.forename: A
authors.initials: A
authors.lastname: Fleig
authors.forename: R
authors.initials: R
authors.lastname: Vennekens
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: J G
authors.initials: JG
authors.lastname: Hoenderop
authors.forename: R J
authors.initials: RJ
authors.lastname: Bindels
authors.forename: G
authors.initials: G
authors.lastname: Droogmans
authors.forename: R
authors.initials: R
authors.lastname: Penner
authors.forename: B
authors.initials: B
authors.lastname: Nilius
mesh_terms: D015220:Calcium Channels / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D018408:Patch-Clamp Techniques; D050916:TRPV Cation Channels
chemical_list: D015220:Calcium Channels; D050916:TRPV Cation Channels; C120776:TRPV6 channel