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Surface expression and function of Cav3.2 T-type calcium channels are controlled by asparagine-linked glycosylation

  • Ion Channels, Receptors and Transporters
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Abstract

Low-voltage-activated T-type calcium channels play important roles in neuronal physiology where they control cellular excitability and synaptic transmission. Alteration in T-type channel expression has been linked to various pathophysiological conditions such as pain arising from diabetic neuropathy. In the present study, we looked at the role of asparagine (N)-linked glycosylation on human Cav3.2 T-type channel expression and function. Manipulation of N-glycans on cells expressing a recombinant Cav3.2 channel revealed that N-linked glycosylation is critical for proper functional expression of the channel. Using site-directed mutagenesis to disrupt the canonical N-linked glycosylation sites of Cav3.2 channel, we show that glycosylation at asparagine N192 is critical for channel expression at the surface, whereas glycosylation at asparagine N1466 controls channel activity. Moreover, we demonstrate that N-linked glycosylation of Cav3.2 not only controls surface expression and activity of the channel but also underlies glucose-dependent potentiation of T-type Ca2+ current. Our data suggest that N-linked glycosylation of T-type channels may play an important role in aberrant upregulation of T-type channel activity in response to glucose elevations.

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Acknowledgments

NW was supported by fellowships from Alberta Innovates—Health Solutions (AIHS) and from the Hotchkiss Brain Institute (HBI). SAGB was supported by the Heart and Stroke Foundation of Canada Research Fellowship. CB was supported by an AIHS and HBI studentship. GWZ is funded by the Canadian Institutes of Health Research and is a Canada Research Chair and AIHS Scientist.

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  1. Hotchkiss Brain Institute, Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Drive N.W, AB, Calgary, T2N 4N1, Canada

    Norbert Weiss, Stefanie A. G. Black, Chris Bladen, Lina Chen & Gerald W. Zamponi

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  1. Norbert Weiss
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  2. Stefanie A. G. Black
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Correspondence to Gerald W. Zamponi.

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Weiss, N., Black, S.A.G., Bladen, C. et al. Surface expression and function of Cav3.2 T-type calcium channels are controlled by asparagine-linked glycosylation. Pflugers Arch - Eur J Physiol 465, 1159–1170 (2013). https://doi.org/10.1007/s00424-013-1259-3

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