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Asparagine-linked glycosylation modifies voltage-dependent gating properties of CaV3.1-T-type Ca2+ channel

  • Yangong Liu
  • Pu Wang
  • Fangfang Ma
  • Mingqi Zheng
  • Gang Liu
  • Shinichiro Kume
  • Tatsuki Kurokawa
  • Katsushige OnoEmail author
Original Paper
  • 49 Downloads

Abstract

T-type channels are low-voltage-activated channels that play a role in the cardiovascular system particularly for pacemaker activity. Glycosylation is one of the most prevalent post-translational modifications in protein. Among various glycosylation types, the most common one is asparagine-linked (N-linked) glycosylation. The aim of this study was to elucidate the roles of N-linked glycosylation for the gating properties of the CaV3.1-T-type Ca2+ channel. N-linked glycosylation synthesis inhibitor tunicamycin causes a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa.T) when applied for 12 h or longer. Tunicamycin (24 h) significantly shifted the activation curve to the depolarization potentials, whereas the steady-state inactivation curve was unaffected. Use-dependent inactivation of CaV3.1-ICa.T was accelerated, and recovery from inactivation was prolonged by tunicamycin (24 h). CaV3.1-ICa.T was insensitive to a glycosidase PNGase F when the channels were expressed on the plasma membrane. These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.

Keywords

Glycosylation T-type Ca2+ channel CaV3.1 α1G channel Tunicamycin 

Notes

Acknowledgements

We are grateful to Ms. Watanabe and Matsuno for their secretary assistance.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Research involving human participants and/or animals

This study does not contain any studies with human participants performed by any of the authors. All procedures performed in studies involving animals were in accordance with the ethical standards of Oita University School of Medicine.

Informed consent

Not applicable.

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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of CardiologyThe First Hospital of Hebei Medical UniversityShijiazhuangPeople’s Republic of China
  2. 2.Department of PathophysiologyOita University School of MedicineYufuJapan

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