title: Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation.
abstract: Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. Currently, little is known about the cellular mechanisms controlling the expression and function of T-type channels. Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. However, the role of N-glycans in the conducting function of T-type channels remains elusive. In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states.
authors.affiliation: a Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences , Bratislava , Slovakia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Ondacova
authors.affiliation: a Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences , Bratislava , Slovakia.
authors.forename: Maria
authors.initials: M
authors.lastname: Karmazinova
authors.affiliation: b Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i. , Prague , Czech Republic.
authors.forename: Joanna
authors.initials: J
authors.lastname: Lazniewska
authors.affiliation: b Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i. , Prague , Czech Republic.
authors.forename: Norbert
authors.initials: N
authors.lastname: Weiss
authors.affiliation: a Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences , Bratislava , Slovakia.
authors.forename: Lubica
authors.initials: L
authors.lastname: Lacinova
mesh_terms: D001216:Asparagine / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000737:chemistry* / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D010539:Permeability
chemical_list: C479952:CACNA1H protein, human; D020747:Calcium Channels, T-Type; D001216:Asparagine
keywords: Cav3.2; T-type channel; calcium channel; gating; glycosylation