|
||
The Journal of General Physiology, Vol 99, 367-390, Copyright © 1992 by The Rockefeller University Press
ARTICLES |
TN Marks and SW Jones
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106.
We have investigated the gating kinetics of calcium channels in the A7r5 cell line at the level of single channels and whole cell currents, in the absence and presence of dihydropyridine (DHP) calcium channel agonists. Although latencies to first opening and macroscopic currents are strongly voltage dependent, analysis of amplitude histograms indicates that the primary open-closed transition is voltage independent. This suggests that the molecular mechanisms for voltage sensing and channel opening are distinct, but coupled. We propose a modified Monod-Wyman-Changeux (MWC) model for channel activation, where movement of a voltage sensor is analogous to ligand binding, and the closed and open channels correspond to inactive (T) and active (R) states. This model can account for the activation kinetics of the calcium channel, and is consistent with the existence of four homologous domains in the main subunit of the calcium channel protein. DHP agonists slow deactivation kinetics, shift the activation curve to more negative potentials with an increase in slope, induce intermingled fast and slow channel openings, and reduce the latency to first opening. These effects are predicted by the MWC model if we make the simple assumption that DHP agonists act as allosteric effectors to stabilize the open states of the channel.
This article has been cited by other articles:
![]() |
E. Polakova, A. Zahradnikova Jr, J. Pavelkova, I. Zahradnik, and A. Zahradnikova Local calcium release activation by DHPR calcium channel openings in rat cardiac myocytes J. Physiol., August 15, 2008; 586(16): 3839 - 3854. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Essin, A. Welling, F. Hofmann, F. C. Luft, M. Gollasch, and S. Moosmang Indirect coupling between Cav1.2 channels and ryanodine receptors to generate Ca2+ sparks in murine arterial smooth muscle cells J. Physiol., October 1, 2007; 584(1): 205 - 219. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Nakayama, Y. Ito, S. Sato, A. Kamijo, H.-N. Liu, and S. Kajioka Tyrosine kinase inhibitors and ATP modulate the conversion of smooth muscle L-type Ca2+ channels toward a second open state FASEB J, July 1, 2006; 20(9): 1492 - 1494. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Chen, H. Kalbacher, and S. Grunder Interaction of Acid-sensing Ion Channel (ASIC) 1 with the Tarantula Toxin Psalmotoxin 1 is State Dependent J. Gen. Physiol., February 27, 2006; 127(3): 267 - 276. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Zahradnik, S. Gyorke, and A. Zahradnikova Calcium Activation of Ryanodine Receptor Channels--Reconciling RyR Gating Models with Tetrameric Channel Structure J. Gen. Physiol., October 31, 2005; 126(5): 515 - 527. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. L. Chapman and A. M.J. VanDongen K Channel Subconductance Levels Result from Heteromeric Pore Conformations J. Gen. Physiol., July 25, 2005; 126(2): 87 - 103. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. I. McDonough, Y. Mori, and B. P. Bean FPL 64176 Modification of CaV1.2 L-Type Calcium Channels: Dissociation of Effects on Ionic Current and Gating Current Biophys. J., January 1, 2005; 88(1): 211 - 223. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. S. Rothberg Allosteric Modulation of Ion Channels: The Case of Maxi-K Sci. Signal., April 6, 2004; 2004(227): pe16 - pe16. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Dzhura and A. Neely Differential Modulation of Cardiac Ca2+ Channel Gating by {beta}-Subunits Biophys. J., July 1, 2003; 85(1): 274 - 289. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Ferreira, E. Rios, and N. Reyes Two Components of Voltage-Dependent Inactivation in Cav1.2 Channels Revealed by Its Gating Currents Biophys. J., June 1, 2003; 84(6): 3662 - 3678. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. L. Magleby Gating Mechanism of BK (Slo1) Channels: So Near, Yet So Far J. Gen. Physiol., February 3, 2003; 121(2): 81 - 96. [Full Text] [PDF] |
||||
![]() |
M. Aoyama, M. Murakami, T. Iwashita, Y. Ito, K. Yamaki, and S. Nakayama Slow Deactivation and U-Shaped Inactivation Properties in Cloned Cav1.2b Channels in Chinese Hamster Ovary Cells Biophys. J., January 1, 2003; 84(1): 709 - 724. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. T. Horrigan and R. W. Aldrich Coupling between Voltage Sensor Activation, Ca2+ Binding and Channel Opening in Large Conductance (BK) Potassium Channels J. Gen. Physiol., August 26, 2002; 120(3): 267 - 305. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. P. Johnson Jr, J. R. Balser, and P. B. Bennett A Novel Extracellular Calcium Sensing Mechanism in Voltage-Gated Potassium Ion Channels J. Neurosci., June 15, 2001; 21(12): 4143 - 4153. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Yamaguchi, J. N. Muth, M. Varadi, A. Schwartz, and G. Varadi Critical role of conserved proline residues in the transmembrane segment 4 voltage sensor function and in the gating of L-type calcium channels PNAS, February 16, 1999; 96(4): 1357 - 1362. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. G. Klemic, D. M. Durand, and S. W. Jones Activation Kinetics of the Delayed Rectifier Potassium Current of Bullfrog Sympathetic Neurons J Neurophysiol, May 1, 1998; 79(5): 2345 - 2357. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Delcour and R. Tsien Altered prevalence of gating modes in neurotransmitter inhibition of N-type calcium channels Science, February 12, 1993; 259(5097): 980 - 984. [Abstract] |
||||
|
|