title: Defective polysialylation and sialylation induce opposite effects on gating of the skeletal Na+ channel NaV1.4 in Chinese hamster ovary cells.
abstract: Polysialic acid (polySia) is a large, negatively charged homopolymer of 2,8-linked N-acetylneuraminic acid residues resulting from remodeling and extension of protein-bound sialic acid (Sia) residues and seems to have a key role in regulating neural cell development and function. The aim of this study was to explore and compare the effects of polySia and sialylation on gating of voltage-gated sodium channels. The skeletal muscle α-subunit NaV1.4 was transiently expressed in wild-type Chinese hamster ovary (CHO) cells or in mutant CHO cells with deficits in their capacity to produce sialylated or polysialylated membrane components. Expression in both mutant cell lines resulted in larger peak current amplitudes as compared to wild-type CHO cells. Loss of Sia and polySia also resulted in significant shifts of voltage-dependent activation and steady-state inactivation, however, in opposite directions. Furthermore, only the loss of Sia had a significant effect on recovery from fast inactivation. Our data demonstrate for the first time that gating of voltage-gated sodium channels seems to be differentially regulated by polySia and Sia.
authors: Clinic for Anaesthesia and Critical Care Medicine, Hannover Medical School, Hannover, Germany. ahrens.j@MH-Hannover.de
authors: Jörg
authors: J
authors: Ahrens
authors: Nilufar
authors: N
authors: Foadi
authors: Ania
authors: A
authors: Eberhardt
authors: Gertrud
authors: G
authors: Haeseler
authors: Reinhard
authors: R
authors: Dengler
authors: Andreas
authors: A
authors: Leffler
authors: Martina
authors: M
authors: Mühlenhoff
authors: Rita
authors: R
authors: Gerardy-Schahn
authors: Martin
authors: M
authors: Leuwer