|
|
|
|
|
|
|
||
The Journal of General Physiology, Vol 103, 447-470, Copyright © 1994 by The Rockefeller University Press
ARTICLES |
RJ French, JF Worley 3rd, WF Wonderlin, AS Kularatna and BK Krueger
Department of Medical Physiology, University of Calgary, Alberta, Canada.
Calcium ions, applied internally, externally, or symmetrically, have been used in conjunction with rate-theory modeling to explore the energy profile of the ion-conducting pore of sodium channels. The block, by extracellular and/or intracellular calcium, of sodium ion conduction through single, batrachotoxin-activated sodium channels from rat brain was studied in planar lipid bilayers. Extracellular calcium caused a reduction of inward current that was enhanced by hyperpolarization and a weaker block of outward current. Intracellular calcium reduced both outward and inward sodium current, with the block being weakly dependent on voltage and enhanced by depolarization. These results, together with the dependence of single-channel conductance on sodium concentration, and the effects of symmetrically applied calcium, were described using single- or double-occupancy, three-barrier, two- site (3B2S), or single-occupancy, 4B3S rate-theory models. There appear to be distinct outer and inner regions of the channel, easily accessed by external or internal calcium respectively, separated by a rate- limiting barrier to calcium permeation. Most of the data could be well fit by each of the models. Reducing the ion interaction energies sufficiently to allow a small but significant probability of two-ion occupancy in the 3B2S model yielded better overall fits than for either 3B2S or 4B3S models constrained to single occupancy. The outer ion- binding site of the model may represent a section of the pore in which sodium, calcium, and guanidinium toxins, such as saxitoxin or tetrodotoxin, compete. Under physiological conditions, with millimolar calcium externally, and high potassium internally, the model channels are occupied by calcium or potassium much of the time, causing a significant reduction in single-channel conductance from the value measured with sodium as the only cation species present. Sodium conductance and degree of block by external calcium are reduced by modification of single channels with the carboxyl reagent, trimethyloxonium (TMO) (Worley et al., 1986) Journal of General Physiology. 87:327-349). Elevations of only the outermost parts of the energy profiles for sodium and calcium were sufficient to account for the reductions in conductance and in efficacy of calcium block produced by TMO modification.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Casini, A. O. Verkerk, M. M.G.J. van Borren, A. C.G. van Ginneken, M. W. Veldkamp, J. M.T. de Bakker, and H. L. Tan Intracellular calcium modulation of voltage-gated sodium channels in ventricular myocytes Cardiovasc Res, January 1, 2009; 81(1): 72 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Ma, E. Pavlov, T. Britvina, G. W. Zamponi, and R. J. French Trans-Channel Interactions in Batrachotoxin-Modified Rat Skeletal Muscle Sodium Channels: Kinetic Analysis of Mutual Inhibition between {micro}-Conotoxin GIIIA Derivatives and Amine Blockers Biophys. J., November 1, 2008; 95(9): 4266 - 4276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Pavlov, T. Britvina, J. R. McArthur, Q. Ma, I. Sierralta, G. W. Zamponi, and R. J. French Trans-Channel Interactions in Batrachotoxin-Modified Skeletal Muscle Sodium Channels: Voltage-Dependent Block by Cytoplasmic Amines, and the Influence of {micro}-Conotoxin GIIIA Derivatives and Permeant Ions Biophys. J., November 1, 2008; 95(9): 4277 - 4288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Li, K. Hui, R. J. French, K. Sato, C. A. Henrikson, G. F. Tomaselli, and E. Marban Dependence of {micro}-Conotoxin Block of Sodium Channels on Ionic Strength but Not on the Permeating [Na+]: IMPLICATIONS FOR THE DISTINCTIVE MECHANISTIC INTERACTIONS BETWEEN Na+ AND K+ CHANNEL PORE-BLOCKING TOXINS AND THEIR MOLECULAR TARGETS J. Biol. Chem., August 15, 2003; 278(33): 30912 - 30919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hui, D. McIntyre, and R. J. French Conotoxins as Sensors of Local pH and Electrostatic Potential in the Outer Vestibule of the Sodium Channel J. Gen. Physiol., June 30, 2003; 122(1): 63 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Guatimosim, E. A. Sobie, J. dos Santos Cruz, L. A. Martin, and W. J. Lederer Molecular identification of a TTX-sensitive Ca2+ current Am J Physiol Cell Physiol, May 1, 2001; 280(5): C1327 - C1339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. B. Nuss, E. Marbán;, C. W. Balke, L. Goldman, R. Aggarwal, S. R. Shorofsky;, J. dos Santos Cruz, L. F. Santana, C. A. Frederick, L. L. Isom, et al. Whether "Slip-Mode Conductance" Occurs Science, April 30, 1999; 284(5415): 711a - 711. [Full Text]
|
|
|
|
|
|
L. F. Santana, A. M. Gómez, and W. J. Lederer Ca2+ Flux Through Promiscuous Cardiac Na+ Channels: Slip-Mode Conductance Science, February 13, 1998; 279(5353): 1027 - 1033. [Abstract] [Full Text]
|
|
|
|
