title: Permeable ions differentially affect gating kinetics and unitary conductance of L-type calcium channels.
abstract: Although ion permeation and gating of L-type Ca(2+) channels are generally considered separate processes controlled by distinct components of the channel protein, ion selectivity can vary with the kinetic state. To test this possibility, we studied single-channel currents (cell-attached) of recombinant L-type channels (Ca(V)1.2, beta(2a), and alpha(2)delta) transiently expressed in tsA201 cells in the presence of the channel agonist BayK 8644 which promotes long channel openings (Mode 2 openings). We found that both the brief (Mode 1) and long (Mode 2) mean open times in the presence of Ca(2+) were relatively longer than those with Ba(2+). The unitary slope conductance with Ba(2+) was significantly larger (p<0.05) in Mode 2 openings than for brief Mode 1 openings, whereas the conductance with Ca(2+) did not vary with mode gating. Consequently, the gamma(Ba):gamma(Ca) ratio was greater for Mode 2 than Mode 1 openings. Our findings indicate that both ion permeation and gating kinetics of the L-type channel are differentially modulated by permeable ions. Ca(2+) binding to the L-type channel may stabilize the alteration of channel ion permeability mediated by gating kinetics, and thus, play a role in preventing excessive ion entry when the activation gating of the channel is promoted to the prolonged open state.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ont., Canada M5S 1A8.
authors.forename: Kwokyin
authors.initials: K
authors.lastname: Hui
authors.forename: Peter
authors.initials: P
authors.lastname: Gardzinski
authors.forename: Hong-Shuo
authors.initials: HS
authors.lastname: Sun
authors.forename: Peter H
authors.initials: PH
authors.lastname: Backx
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Feng
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D001464:Barium / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004553:Electric Conductivity; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007477:Ions; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D007477:Ions; D001464:Barium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium