|
|
|
|
|
|
|
||
The Journal of General Physiology, Vol 102, 1057-1083, Copyright © 1993 by The Rockefeller University Press
ARTICLES |
J Tseng-Crank, JA Yao, MF Berman and GN Tseng
Molecular Biology Department, Glaxo Incorporated Research Institute, Research Triangle Park, North Carolina 27709.
It has been shown for a Shaker channel (H-4) that its NH2-terminal cytoplasmic domain may form a "ball and chain" structure, with the "chain" tethering the "ball" to the channel while the "ball" capable of binding to the channel in its open state and causing inactivation. Equivalent structures have not been identified in mammalian Shaker homologues. We studied the functional role of the NH2-terminal region of a fast-inactivating mammalian K channel, RHK1 (Kv1.4), by deleting different domains in this region and examining the resultant changes in channel properties at whole cell and single channel levels. Deleting the NH2-terminal hydrophobic domain (domain A) or the subsequent positive charges (domain I) from RHK1 greatly slowed the decay of whole cell currents, suggesting the existence of a ball-like structure in RHK1 similar to that in the Shaker channel. The function of the ball appeared to be abolished by deleting domain A, while modified but maintained by deleting domain I. In the latter case, the data suggest that the positive charges needed for the function of the ball can be replaced by amino acids from a following region (domain III) that has a high positive charge density. Deleting multiple domains from the NH2 terminus of RHK1 corresponding to the chain in Shaker H-4 did not induce expected changes in channel properties that might result from a shortening of a chain. A comparison of single channel kinetics of selected mutant channels with those of the wild-type channel indicated that these deletion mutations slowed whole cell currents by prolonging burst durations and by increasing the probability of reopening during depolarization. There were no changes in single channel current amplitude or latency to first opening. In conclusion, our observations indicate that the inactivation mechanism of RHK1 is similar to that of Shaker H-4 in that a positively charged cytoplasmic domain is important for such a process. The NH2-terminal domain is not involved in channel activation or ion permeation process.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S.-Q. Cai and F. Sesti A New Mode of Regulation of N-type Inactivation in a Caenorhabditis elegans Voltage-gated Potassium Channel J. Biol. Chem., June 22, 2007; 282(25): 18597 - 18601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Weng, Y. Cao, N. Moss, and M. Zhou Modulation of Voltage-dependent Shaker Family Potassium Channels by an Aldo-Keto Reductase J. Biol. Chem., June 2, 2006; 281(22): 15194 - 15200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. McAlear, X. Liu, J. B. Williams, C. M. McNicholas-Bevensee, and M. O. Bevensee Electrogenic Na/HCO3 Cotransporter (NBCe1) Variants Expressed in Xenopus Oocytes: Functional Comparison and Roles of the Amino and Carboxy Termini J. Gen. Physiol., May 30, 2006; 127(6): 639 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hatano, S. Ohya, K. Muraki, R. B. Clark, W. R. Giles, and Y. Imaizumi Two Arginines in the Cytoplasmic C-terminal Domain Are Essential for Voltage-dependent Regulation of A-type K+ Current in the Kv4 Channel Subfamily J. Biol. Chem., February 13, 2004; 279(7): 5450 - 5459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-M. Xia, J.P. Ding, and C. J. Lingle Inactivation of BK Channels by the NH2 Terminus of the {beta}2 Auxiliary Subunit: An Essential Role of a Terminal Peptide Segment of Three Hydrophobic Residues J. Gen. Physiol., February 3, 2003; 121(2): 125 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Padanilam, T. Lu, T. Hoshi, B. A. Padanilam, E. F. Shibata, and H.-C. Lee Molecular Determinants of Intracellular pH Modulation of Human Kv1.4 N-Type Inactivation Mol. Pharmacol., July 1, 2002; 62(1): 127 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hashimoto, K. Nunoki, H. Kudo, K. Ishii, N. Taira, and T. Yanagisawa Changes in the Inactivation of Rat Kv1.4 K+ Channels Induced by Varying the Number of Inactivation Particles J. Biol. Chem., March 24, 2000; 275(13): 9358 - 9362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-N. Tseng Different State Dependencies of 4-Aminopyridine Binding to rKv1.4 and rKv4.2: Role of the Cytoplasmic Halves of the Fifth and Sixth Transmembrane Segments J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 569 - 577. [Abstract] [Full Text]
|
|
|
|
|
|
H. Zhang, B. Zhu, J.-A. Yao, and G.-N. Tseng Differential Effects of S6 Mutations on Binding of Quinidine and 4-Aminopyridine to Rat Isoform of Kv1.4: Common Site but Different Factors in Determining Blockers' Binding Affinity J. Pharmacol. Exp. Ther., October 1, 1998; 287(1): 332 - 343. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. L. Rasmusson, M. J. Morales, S. Wang, S. Liu, D. L. Campbell, M. V. Brahmajothi, and H. C. Strauss Inactivation of Voltage-Gated Cardiac K+ Channels Circ. Res., April 20, 1998; 82(7): 739 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jiang, J. Tseng-Crank, and G.-N. Tseng Suppression of Slow Delayed Rectifier Current by a Truncated Isoform of KvLQT1 Cloned from Normal Human Heart J. Biol. Chem., September 26, 1997; 272(39): 24109 - 24112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Kondoh, K. Ishii, Y. Nakamura, and N. Taira A Mammalian Transient Type K+ Channel, Rat Kv1.4, Has Two Potential Domains That Could Produce Rapid Inactivation J. Biol. Chem., August 1, 1997; 272(31): 19333 - 19338. [Abstract] [Full Text] [PDF]
|
|
|
|
