How do T-type calcium channels control low-threshold exocytosis?

Abstract

Low-voltage-activated T-type calcium channels act as a major pathway for calcium entry near the resting membrane potential in a wide range of neuronal cell types. Several reports have uncovered an unrecognized feature of T-type channels in the control of vesicular neurotransmitter and hormone release, a process so far thought to be mediated exclusively by high-voltage-activated calcium channels. However, the underlying molecular mechanisms linking T-type calcium channels to vesicular exocytosis have remained enigmatic. In a recent study, we have reported that Ca_v3.2 T-type channel forms a signaling complex with the neuronal Q-SNARE syntaxin-1A and SNAP-25. This interaction that relies on specific Ca_v3.2 molecular determinants, not only modulates T-type channel activity, but was also found essential to support low-threshold exocytosis upon Ca_v3.2 channel expression in MPC 9/3L-AH chromaffin cells. Overall, we have indentified an unrecognized regulation pathway of T-type calcium channels by SNARE proteins, and proposed the first molecular mechanism by which T-type channels could mediate low-threshold exocytosis.

Keywords: :

• Ca_v3.2 channel
• calcium channel
• chromaffin cell
• exocytosis
• MPC cell
• neuron
• SNAP-25
• SNARE
• syntaxin-1A
• T-type

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Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

N.W is supported by a postdoctoral fellowship from Alberta Innovates Health Solutions (AIHS) and Hotchkiss Brain Institute. G.W.Z is funded by the Canadian Institutes of Health Research, is a Canada Research Chair and AIHS Scientist.