|
|
|
|
|
|
|
||
ARTICLE |
Correspondence to Jian Yang: jy160{at}columbia.edu
Ion channels open and close in response to changes in transmembrane voltage or ligand concentration. Recent studies show that K+ channels possess two gates, one at the intracellular end of the pore and the other at the selectivity filter. In this study we determined the location of the activation gate in a voltage-gated Ca2+ channel (VGCC) by examining the open/closed state dependence of the rate of modification by intracellular methanethiosulfonate ethyltrimethylammonium (MTSET) of pore-lining cysteines engineered in the S6 segments of the 
1 subunit of P/Q type Ca2+ channels. We found that positions above the putative membrane/cytoplasm interface, including two positions below the corresponding S6 bundle crossing in K+ channels, showed pronounced state-dependent accessibility to internal MTSET, reacting 
1,000-fold faster with MTSET in the open state than in the closed state. In contrast, a position at or below the putative membrane/cytoplasm interface was modified equally rapidly in both the open and closed states. Our results suggest that the S6 helices of the 1 subunit of VGCCs undergo conformation changes during gating and the activation gate is located at the intracellular end of the pore.
Abbreviations used in this paper: CNG, cyclic nucleotide–gated; MTSET, methanethiosulfonate ethyltrimethylammonium; VGCC, voltage-gated Ca2+ channel.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
Related Article
This article has been cited by other articles:
|
|
 |
|
  Y. Zhang, Y.-h. Chen, S. D. Bangaru, L. He, K. Abele, S. Tanabe, T. Kozasa, and J. Yang Origin of the Voltage Dependence of G-Protein Regulation of P/Q-type Ca2+ Channels J. Neurosci., December 24, 2008; 28(52): 14176 - 14188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-R. Chang and C.-C. Kuo The Activation Gate and Gating Mechanism of the NMDA Receptor J. Neurosci., February 13, 2008; 28(7): 1546 - 1556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bruening-Wright, W.-S. Lee, J. P. Adelman, and J. Maylie Evidence for a Deep Pore Activation Gate in Small Conductance Ca2+-activated K+ Channels J. Gen. Physiol., November 26, 2007; 130(6): 601 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Raybaud, E.-E. Baspinar, F. Dionne, Y. Dodier, R. Sauve, and L. Parent The Role of Distal S6 Hydrophobic Residues in the Voltage-dependent Gating of CaV2.3 Channels J. Biol. Chem., September 21, 2007; 282(38): 27944 - 27952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Berkefeld, C. A. Sailer, W. Bildl, V. Rohde, J.-O. Thumfart, S. Eble, N. Klugbauer, E. Reisinger, J. Bischofberger, D. Oliver, et al. BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling. Science, October 27, 2006; 314(5799): 615 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Erxleben, Y. Liao, S. Gentile, D. Chin, C. Gomez-Alegria, Y. Mori, L. Birnbaumer, and D. L. Armstrong Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices. PNAS, March 7, 2006; 103(10): 3932 - 3937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Highlights from the Literature Physiology, December 1, 2005; 20(6): 369 - 373. [Full Text] [PDF]
|
|
|
|
|
|
X.-g. Zhen, C. Xie, A. Fitzmaurice, C. E. Schoonover, E. T. Orenstein, and J. Yang Functional Architecture of the Inner Pore of a Voltage-gated Ca2+ Channel J. Gen. Physiol., August 29, 2005; 126(3): 193 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
