Contribution of the NH2 terminus of Kv2.1 to channel activation

The American Journal of Physiology
J M PascualA M Brown

Abstract

Opening and closing of voltage-operated channels requires the interaction of diverse structural elements. One approach to the identification of channel domains that participate in gating is to locate the sites of action of modifiers. Covalent reaction of Kv2.1 channels with the neutral, sulfhydryl-specific methylmethanethiosulfonate (MMTS) caused a slowing of channel gating with a predominant effect on the kinetics of activation. These effects were also obtained after intracellular, but not extracellular, application of a charged MMTS analog. Single channel analysis revealed that MMTS acted primarily by prolonging the latency to first opening without substantially affecting gating transitions after the channel first opens and until it inactivates. To localize the channel cysteine(s) with which MMTS reacts, we generated NH2- and COOH-terminal deletion mutants and a construct in which all three cysteines in transmembrane regions were substituted. Only the NH2-terminal deletion construct gave rise to currents that activated slowly and displayed MMTS-insensitive kinetics. These results show that the NH2-terminal tail of Kv2.1 participates in transitions leading to activation through interactions involving reduced cysteine(s) that c...Continue Reading

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Citations

Oct 16, 2004·The Journal of Biological Chemistry·Kumud KunjilwarPaul J Pfaffinger
May 8, 2003·European Biophysics Journal : EBJ·Anurag Varshney, M K Mathew
Mar 19, 2003·The Journal of Biological Chemistry·Daniel KerschensteinerMartin Stocker
Aug 24, 2010·Nature Structural & Molecular Biology·Zhenming XuPaolo Casali
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Feb 1, 2003·The Journal of Biological Chemistry·Min JuDennis Wray
Jun 16, 2005·The Journal of General Physiology·Guangyu WangManuel Covarrubias
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Apr 1, 2015·The Journal of Comparative Neurology·Ryan E Tooker, Jozsef Vigh
Jul 31, 2003·Progress in Biophysics and Molecular Biology·Anurag Varshney, M K Mathew
Jun 14, 2005·Neurotoxicology·Hiroaki MisonouJames S Trimmer

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