α2δ‐2 is required for depolarization‐induced suppression of excitation in Purkinje cells
Abstract
α2δ proteins (CACNA2D1–4) are required for normal neurological function and contribute to membrane trafficking of voltage‐gated calcium channels, through which calcium entry initiates numerous physiological processes. However, it remains unclear how α2δ proteins influence calcium‐mediated signalling to control neuronal output. Using whole‐cell recordings of mouse Purkinje cells, we show that α2δ‐2 is required for functional coupling of postsynaptic voltage‐dependent calcium entry with calcium‐dependent effector mechanisms controlling two different outputs, depolarization‐induced suppression of excitation and spike afterhyperpolarization. Our findings indicate an important role for α2δ‐2 proteins in regulating functional postsynaptic calcium channel coupling in neurons, providing new context for understanding the effects of α2δ mutations on neuronal circuit function and presenting additional potential avenues to manipulate α2δ‐mediated signalling for therapeutic gain.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 03, 2021
- Source ID
- 10.1113/jp282438
Entities
People
- Eric Schnell
- Gary L Westbrook
- Kathleen A Beeson
Organizations
- National Institute of Neurological Disorders and Stroke
- National Institutes of Health
- Oregon Health & Science University
- United States Department of Defense
- United States Department of Veterans Affairs