Selective inhibition of neuronal Ca(v)3.3 T-type calcium channels by TAT-based channel peptide

Low-voltage-activated Ca(v)3 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 Ca(v)3.3 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 Ca(v)3 channels. We show that chronic application of TAT-C3P on tsA-201 cells expressing Ca(v)3 channels selectively inhibits Ca(v)3.3 channels without affecting Ca(v)3.1 and Ca(v)3.2 channels. Therefore, the TAT-C3P peptide described in this study represents a new tool to address the specific physiological role of Ca(v)3.3 channels, and to potentially enhance our understanding of Ca(v)3.3 in disease.