Permeable ions differentially affect gating kinetics and unitary conductance of L-type calcium channels

• Published in: Biochemical and biophysical research communications 2005-12, Vol.338 (2), p.783-792
• Main Authors: Hui, Kwokyin, Gardzinski, Peter, Sun, Hong-Shuo, Backx, Peter H., Feng, Zhong-Ping
• Format: Article
• Language: English
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Barium; Barium - metabolism; BayK 8644; Calcium; Calcium - metabolism; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - physiology; Cell Line; Cell Membrane Permeability - drug effects; Cell Membrane Permeability - physiology; Electric Conductivity; Gating; Humans; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Ion permeation; Ions; Kidney - drug effects; Kidney - metabolism; Kinetics; L-type calcium channels; Membrane Potentials - drug effects; Membrane Potentials - physiology; Patch clamp recording; Unitary conductance
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.10.014

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 V1.2, β 2a, and α 2δ) 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 γ Ba: γ 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.