|
|
|
|
|
|
|
||
From the Department of Physiology and Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut
06030
To identify regions of the ryanodine receptor (RyR) important for ion conduction we modified the
channel with sulfhydryl-reacting compounds. After addition of methanethiosulfonate (MTS) compounds channel
conductance was decreased while other channel properties, including channel regulation by ATP, caffeine, or Ca,
were unaffected. The site of action was accessible to the MTS compounds from the cytoplasmic, but not the luminal, side of the channel. In addition, the hydrophilic MTS compounds were only effective when the channel was
open, suggesting that the compounds covalently modify the channel from within the water-filled ion conducting
pathway. The decrease in channel current amplitude occurred in a step-wise fashion and was irreversible and cumulative over time, eventually leading to the complete block of channel current. However, the time required for
each consecutive modification during continuous exposure to the MTS compounds increased, suggesting that
successive modification by the MTS compounds is not independent. These results are consistent with the hypothesis that the channel forms a wide vestibule on the cytoplasmic side and contains a much smaller opening on the
luminal side. Furthermore, our results indicate that the MTS compounds can serve as functional markers for specific residues of the RyR to be identified in molecular studies.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. I. Anyatonwu and B. E. Ehrlich Organic Cation Permeation through the Channel Formed by Polycystin-2 J. Biol. Chem., August 19, 2005; 280(33): 29488 - 29493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. I. Anyatonwu, E. D. Buck, and B. E. Ehrlich Methanethiosulfonate Ethylammonium Block of Amine Currents through the Ryanodine Receptor Reveals Single Pore Architecture J. Biol. Chem., November 14, 2003; 278(46): 45528 - 45538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Feng, G. Liu, R. Xia, J. J. Abramson, and I. N. Pessah Site-Selective Modification of Hyperreactive Cysteines of Ryanodine Receptor Complex by Quinones Mol. Pharmacol., May 1, 1999; 55(5): 821 - 831. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. Oba, T. Ishikawa, and M. Yamaguchi Sulfhydryls associated with H2O2-induced channel activation are on luminal side of ryanodine receptors Am J Physiol Cell Physiol, April 1, 1998; 274(4): C914 - C921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Quinn, L. Castellani, K. Ondrias, and B. E. Ehrlich Characterization of the ryanodine receptor/channel of invertebrate muscle Am J Physiol Regulatory Integrative Comp Physiol, February 1, 1998; 274(2): R494 - R502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Koch, I. Bodi, A. Schwartz, and G. Varadi Architecture of Ca2+ Channel Pore-lining Segments Revealed by Covalent Modification of Substituted Cysteines J. Biol. Chem., October 27, 2000; 275(44): 34493 - 34500. [Abstract] [Full Text] [PDF]
|
|
|
|
