Universität zu Köln

Despang, Patrick, Salamon, Sarah ORCID: 0009-0005-7435-405X, Breitenkamp, Alexandra, Kuzmenkina, Elza and Matthes, Jan ORCID: 0000-0003-2754-1555 (2022). Inhibitory effects on L- and N-type calcium channels by a novel Ca-V beta(1) variant identified in a patient with autism spectrum disorder. Naunyn-Schmiedebergs Arch. Pharmacol., 395 (4). S. 459 - 471. NEW YORK: SPRINGER. ISSN 1432-1912

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Abstract

Voltage-gated calcium channel (VGCC) subunits have been genetically associated with autism spectrum disorders (ASD). The properties of the pore-forming VGCC subunit are modulated by auxiliary beta-subunits, which exist in four isoforms (Ca-V beta(1-4)). Our previous findings suggested that activation of L-type VGCCs is a common feature of Ca-V beta(2) subunit mutations found in ASD patients. In the current study, we functionally characterized a novel Ca-V beta(1b) variant (p.R296C) identified in an ASD patient. We used whole-cell and single-channel patch clamp to study the effect of Ca-V beta(1b_R296C) on the function of L- and N-type VGCCs. Furthermore, we used co-immunoprecipitation followed by Western blot to evaluate the interaction of the Ca-V beta(1b)-subunits with the RGK-protein Gem. Our data obtained at both, whole-cell and single-channel levels, show that compared to a wild-type Ca-V beta(1b), the Ca-V beta(1b_R296C) variant inhibits L- and N-type VGCCs. Interaction with and modulation by the RGK-protein Gem seems to be intact. Our findings indicate functional effects of the Ca-V beta(1b_R296C) variant differing from that attributed to Ca-V beta(2) variants found in ASD patients. Further studies have to detail the effects on different VGCC subtypes and on VGCC expression.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Despang, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Salamon, Sarah UNSPECIFIED orcid.org/0009-0005-7435-405X UNSPECIFIED Breitenkamp, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuzmenkina, Elza UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthes, Jan UNSPECIFIED orcid.org/0000-0003-2754-1555 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-660597
DOI:	10.1007/s00210-022-02213-7
Journal or Publication Title:	Naunyn-Schmiedebergs Arch. Pharmacol.
Volume:	395
Number:	4
Page Range:	S. 459 - 471
Date:	2022
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1912
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BETA-SUBUNIT; MODULATION; HETEROGENEITY; MECHANISM; DOMAIN; SERVER Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66059