Selective inhibition of neuronal Cav3.3 T-type calcium channels by TAT-based channel peptide

Mol Brain. 2020 Jun 19;13(1):95. doi: 10.1186/s13041-020-00636-y.

Abstract

Low-voltage-activated Cav3 calcium channels (T-type) play an essential role in the functioning of the nervous system where they support oscillatory activities that relie on several channel molecular determinants that shape their unique gating properties. In a previous study, we documented the important role of the carboxy proximal region in the functioning of Cav3.3 channels. Here, we explore the ability of a TAT-based cell penetrating peptide containing this carboxy proximal region (TAT-C3P) to modulate the activity of Cav3 channels. We show that chronic application of TAT-C3P on tsA-201 cells expressing Cav3 channels selectively inhibits Cav3.3 channels without affecting Cav3.1 and Cav3.2 channels. Therefore, the TAT-C3P peptide described in this study represents a new tool to address the specific physiological role of Cav3.3 channels, and to potentially enhance our understanding of Cav3.3 in disease.

Keywords: Calcium channel; Cav3.3 channel; Inhibitor; T-type channel; TAT-peptide.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium Channels, T-Type / chemistry
  • Calcium Channels, T-Type / metabolism*
  • Cell Line
  • Humans
  • Models, Molecular
  • Neurons / metabolism*
  • Peptides / metabolism*

Substances

  • Calcium Channels, T-Type
  • Peptides