PMID: 7971148Jul 1, 1994Paper

Insertion mutations of the RIIA Na+ channel reveal novel features of voltage gating and protein kinase A modulation

Pflügers Archiv : European journal of physiology
T E HebertR J Dunn

Abstract

A linker insertion mutagenesis strategy was developed to probe functional subdomains of the RIIA Na+ channel alpha-subunit. We describe mutations within the first two repeat domains that provide new functional information for three segments of the channel structure. 1. The insertion of two alanine residues within the short peptide segment joining helices S4 and S5 in domain II had two effects: a depolarizing shift of steady-state activation and reduced single-channel currents. These results suggest that the peptide segment following the S4 voltage sensor is involved in the activation process and is facing the ion pore. 2. An insertion immediately N-terminal to the proposed transmembrane helix S1 in domain II shifted the steady-state activation in the depolarizing direction, suggesting a functional role in channel gating. 3. Insertions in the large, cytoplasmic loop between domains I and II affect two channel functions: inactivation and protein kinase A modulation. These results demonstrate that the linker insertion approach can provide novel insights into the structure-function relationships of large, multi-domain ion channel proteins.

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Citations

Dec 3, 2008·European Journal of Pharmacology·Abdellah AhnaouWilhelmus H I M Drinkenburg
Mar 9, 2007·Journal of Neurophysiology·Cédric YvonJürg Streit

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