|
|
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The Journal of General Physiology, Vol 95, 911-939, Copyright © 1990 by The Rockefeller University Press
ARTICLES |
DT Yue and E Marban
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
We investigated the mechanism whereby ions cross dihydropyridine- sensitive (L-type) Ca channels in guinea pig ventricular myocytes. At the single-channel level, we found no evidence of an anomalous mole- fraction effect like that reported previously for whole-cell currents in mixtures of Ba and Ca. With the total concentration of Ba + Ca kept constant at 10 (or 110) mM, neither conductance nor absolute unitary current exhibits a paradoxical decrease when Ba and Ca are mixed, thereby weakening the evidence for a multi-ion permeation scheme. We therefore sought independent evidence to support or reject the multi- ion nature of the L-type Ca channel by measuring conductance at various permeant ion concentrations. Contrary to the predictions of models with only one binding site in the permeation pathway, single-channel conductance does not follow Michaelis-Menten kinetics as Ba activity is increased over three orders of magnitude. Two-fold variation in the Debye length of permeant ion solutions has little effect on conductance, making it unlikely that local surface charge effects could account for these results. Instead, the marked deviation from Michaelis- Menten behavior was best explained by supposing that the permeation pathway contains three or more binding sites that can be occupied simultaneously. The presence of three sites helps explain both a continued rise in conductance as [Ba2+] is increased above 110 mM, and the high single-channel conductance (approximately 7 pS) with 1 mM [Ba2+] as the charge carrier; the latter feature enables the L-type channel to carry surprisingly large currents at physiological divalent cation concentrations. Thus, despite the absence of an anomalous mole- fraction effect between Ba and Ca, we suggest that the L-type Ca channel in heart cells supports ion flux by a single-file, multi-ion permeation mechanism.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Rodriguez-Contreras, P. Lv, J. Zhu, H. J. Kim, and E. N. Yamoah Effects of Strontium on the Permeation and Gating Phenotype of Calcium Channels in Hair Cells J Neurophysiol, October 1, 2008; 100(4): 2115 - 2124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gillespie and D. Boda The Anomalous Mole Fraction Effect in Calcium Channels: A Measure of Preferential Selectivity Biophys. J., September 15, 2008; 95(6): 2658 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Gillespie, D. Boda, Y. He, P. Apel, and Z. S. Siwy Synthetic Nanopores as a Test Case for Ion Channel Theories: The Anomalous Mole Fraction Effect without Single Filing Biophys. J., July 15, 2008; 95(2): 609 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-S. Sun, K. Hui, D. W. K. Lee, and Z.-P. Feng Zn2+ Sensitivity of High- and Low-Voltage Activated Calcium Channels Biophys. J., August 15, 2007; 93(4): 1175 - 1183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shen, D. Yu, H. Hiel, P. Liao, D. T. Yue, P. A. Fuchs, and T. W. Soong Alternative Splicing of the CaV1.3 Channel IQ Domain, a Molecular Switch for Ca2+-Dependent Inactivation within Auditory Hair Cells. J. Neurosci., October 18, 2006; 26(42): 10690 - 10699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Z. Peterson and W. A. Catterall Allosteric Interactions Required for High-Affinity Binding of Dihydropyridine Antagonists to CaV1.1 Channels Are Modulated by Calcium in the Pore Mol. Pharmacol., August 1, 2006; 70(2): 667 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Aromataris, M. L. Roberts, G. J. Barritt, and G. Y. Rychkov Glucagon activates Ca2+ and Cl- channels in rat hepatocytes J. Physiol., June 15, 2006; 573(3): 611 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Greenstein, R. Hinch, and R. L. Winslow Mechanisms of Excitation-Contraction Coupling in an Integrative Model of the Cardiac Ventricular Myocyte Biophys. J., January 1, 2006; 90(1): 77 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, T. A. Ponoran, R. L. Rasmusson, D. S. Ragsdale, and B. Z. Peterson Amino Acid Substitutions in the Pore of the CaV1.2 Calcium Channel Reduce Barium Currents without Affecting Calcium Currents Biophys. J., September 1, 2005; 89(3): 1731 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Perrier, R. Perrier, S. Richard, and J.-P. Benitah Ca2+ Controls Functional Expression of the Cardiac K+ Transient Outward Current via the Calcineurin Pathway J. Biol. Chem., September 24, 2004; 279(39): 40634 - 40639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schubert, U. Krien, I. Wulfsen, D. Schiemann, G. Lehmann, N. Ulfig, R. W. Veh, J. R. Schwarz, and H. Gago Nitric Oxide Donor Sodium Nitroprusside Dilates Rat Small Arteries by Activation of Inward Rectifier Potassium Channels Hypertension, April 1, 2004; 43(4): 891 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rodriguez-Contreras and E. N. Yamoah Effects of Permeant Ion Concentrations on the Gating of L-Type Ca2+ Channels in Hair Cells Biophys. J., May 1, 2003; 84(5): 3457 - 3469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Cibulsky and W. A. Sather Control of Ion Conduction in L-type Ca2+ Channels by the Concerted Action of S5-6 Regions Biophys. J., March 1, 2003; 84(3): 1709 - 1719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Greenstein and R. L. Winslow An Integrative Model of the Cardiac Ventricular Myocyte Incorporating Local Control of Ca2+ Release Biophys. J., December 1, 2002; 83(6): 2918 - 2945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Talavera, M. Staes, A. Janssens, N. Klugbauer, G. Droogmans, F. Hofmann, and B. Nilius Aspartate Residues of the Glu-Glu-Asp-Asp (EEDD) Pore Locus Control Selectivity and Permeation of the T-type Ca2+ Channel alpha 1G J. Biol. Chem., November 30, 2001; 276(49): 45628 - 45635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wakamori, M. Strobeck, T. Niidome, T. Teramoto, K. Imoto, and Y. Mori Functional Characterization of Ion Permeation Pathway in the N-Type Ca2+ Channel J Neurophysiol, February 1, 1998; 79(2): 622 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Handrock, F. Schroder, S. Hirt, A. Haverich, C. Mittmann, and S. Herzig Single-channel properties of L-type calcium channels from failing human ventricle Cardiovasc Res, February 1, 1998; 37(2): 445 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Lambert, Y. Maulet, J. Mouton, R. Beattie, S. Volsen, M. De Waard, and A. Feltz T-Type Ca2+ Current Properties Are Not Modified by Ca2+ Channel beta Subunit Depletion in Nodosus Ganglion Neurons J. Neurosci., September 1, 1997; 17(17): 6621 - 6628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bourinet, G. W. Zamponi, A. Stea, T. W. Soong, B. A. Lewis, L. P. Jones, D. T. Yue, and T. P. Snutch The alpha 1E Calcium Channel Exhibits Permeation Properties Similar to Low-Voltage-Activated Calcium Channels J. Neurosci., August 15, 1996; 16(16): 4983 - 4993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Backx, D. Yue, J. Lawrence, E Marban, and G. Tomaselli Molecular localization of an ion-binding site within the pore of mammalian sodium channels Science, July 10, 1992; 257(5067): 248 - 251. [Abstract] [PDF]
|
|
|
|
|
|
D. Yue, P. Backx, and J. Imredy Calcium-sensitive inactivation in the gating of single calcium channels Science, December 21, 1990; 250(4988): 1735 - 1738. [Abstract] [PDF]
|
|
|
|
|
|
A. Rodriguez-Contreras, W. Nonner, and E. N. Yamoah Ca2+ transport properties and determinants of anomalous mole fraction effects of single voltage-gated Ca2+ channels in hair cells from bullfrog saccule J. Physiol., February 1, 2002; 538(3): 729 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
