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Author(s): WEST JW; PATTON DE; SCHEUER T; WANG YL; GOLDIN AL; CATTERALL WA
Title: A CLUSTER OF HYDROPHOBIC AMINO-ACID-RESIDUES REQUIRED FOR FAST NA+- CHANNEL INACTIVATION
Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89 (22): 10910-10914
Date: 1992 NOV 15
Document Type: Journal : Article
DOI:
Language: English
Comment:
Address: UNIV CALIF IRVINE,DEPT MICROBIOL & MOLEC GENET,IRVINE,CA 92717.
Reprint: WEST, JW, UNIV WASHINGTON,DEPT PHARMACOL,SJ-30,SEATTLE,WA 98195.
E-mail:
Abstract: The inward Na+ current underlying the action potential in nerve is terminated by inactivation. The preceding report shows that deletions within the intracellular linker between domains III and IV remove inactivation, but mutation of conserved basic and paired acidic amino acids has little effect. Here we show that substitution of glutamine for three clustered hydrophobic amino acids, Ile-1488, Phe-1489, and Met-1490, completely removes fast inactivation. Substitution of Met-1490 alone slows inactivation significantly, substitution of Ile-1488 alone both slows inactivation and makes it incomplete, and substitution of Phe-1489 alone removes inactivation nearly completely. These results demonstrate an essential role of Phe-1489 in Na+-channel inactivation. It is proposed that the hydrophobic cluster of Ile-1488, Phe-1489, and Met-1490 serves as a hydrophobic latch that stabilizes the inactivated state in a hinged-lid mechanism of Na+-channel inactivation.
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