A naturally occurring amino acid substitution in the voltage-dependent sodium channel selectivity filter affects channel gating

Wu, Mingming and Ye, Na and Sengupta, Biswa and Zakon, Harold H (2013) A naturally occurring amino acid substitution in the voltage-dependent sodium channel selectivity filter affects channel gating. In: JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY, 199 (10). pp. 829-842.

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Abstract

The pore of sodium channels contains a selectivity filter made of 4 amino acids, D/E/K/A. In voltage sensitive sodium channel (Nav) channels from jellyfish to human the fourth amino acid is Ala. This Ala, when mutated to Asp, promotes slow inactivation. In some Nav channels of pufferfishes, the Ala is replaced with Gly. We studied the biophysical properties of an Ala-to-Gly substitution (A1529G) in rat Nav1.4 channel expressed in Xenopus oocytes alone or with a beta 1 subunit. The Ala-to-Gly substitution does not affect monovalent cation selectivity and positively shifts the voltage-dependent inactivation curve, although co-expression with a beta 1 subunit eliminates the difference between A1529G and WT. There is almost no difference in channel fast inactivation, but the beta 1 subunit accelerates WT current inactivation significantly more than it does the A1529G channels. The Ala-to-Gly substitution mainly influences the rate of recovery from slow inactivation. Again, the beta 1 subunit is less effective on speeding recovery of A1529G than the WT. We searched Nav channels in numerous databases and noted at least four other independent Ala-to-Gly substitutions in Nav channels in teleost fishes. Thus, the Ala-to-Gly substitution occurs more frequently than previously realized, possibly under selection for alterations of channel gating.

Item Type:	Journal Article
Publication:	JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY
Publisher:	SPRINGER
Additional Information:	copy right of this article belongs to Springer Link
Keywords:	Voltage-gated sodium channel; A1529G; Slow inactivation; Selectivity filter
Department/Centre:	Division of Biological Sciences > Centre for Neuroscience
Date Deposited:	25 Oct 2013 14:54
Last Modified:	25 Oct 2013 14:54
URI:	http://eprints.iisc.ac.in/id/eprint/47572

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