Kinetic analysis of block of open sodium channels by a peptide containing the isoleucine, phenylalanine, and methionine (IFM) motif from the inactivation gate

The Journal of General Physiology
G EaholtzW A Catterall

Abstract

We analyzed the kinetics of interaction between the peptide KIFMK, containing the isoleucine, phen-ylalanine, and methionine (IFM) motif from the inactivation gate, and the brain type IIA sodium channels with a mutation that disrupts inactivation (F1489Q). The on-rate constant was concentration dependent, consistent with a bimolecular reaction with open sodium channels, while the off rates were unaffected by changes in the KIFMK concentration. The apparent Kd was approximately 33 microM at 0 mV. The on rates were voltage dependent, supporting the hypothesis that one or both of the charges in KIFMK enter the membrane electric field. The voltage dependence of block was consistent with the equivalent movement of approximately 0.6 electronic charges across the membrane. In contrast, the off rates were voltage independent. The results are consistent with the hypothesis that the KIFMK peptide enters the pore of the open sodium channel from the intracellular side and blocks it.

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Citations

Sep 29, 2011·Cellular and Molecular Life Sciences : CMLS·Mitchell Goldfarb
Mar 15, 2002·The Journal of Peptide Research : Official Journal of the American Peptide Society·Y MaedaY Kuroda
Jan 28, 2004·The Journal of General Physiology·Howard K MotoikeRobert S Kass
Nov 15, 2006·Annals of Medicine·Tamara T KoopmannArthur A M Wilde
Jul 22, 2008·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Xing-Hua FengYong-Hua Ji
Sep 5, 2012·ChemMedChem·Antonio NardiAchim Kless
Mar 2, 2005·Biochemical and Biophysical Research Communications·Sho-Ya Wang, Ging Kuo Wang
Sep 27, 2005·Physiological Reviews·Werner Ulbricht
Jul 30, 2002·The Journal of Biological Chemistry·Toshiyuki KohnoKazuki Sato
Sep 25, 2015·Physiological Reviews·Murali Prakriya, Richard S Lewis
Nov 23, 2018·Biochimica Et Biophysica Acta. Biomembranes·Rolando Guidelli, Lucia Becucci
Jan 20, 1999·Biochemistry·C A RohlR E Klevit

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