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α2δ‐2 is required for depolarization‐induced suppression of excitation in Purkinje cells
Author(s) -
Beeson Kathleen A.,
Westbrook Gary L.,
Schnell Eric
Publication year - 2021
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp282438
Subject(s) - afterhyperpolarization , postsynaptic potential , neuroscience , depolarization , calcium signaling , p type calcium channel , microbiology and biotechnology , calcium , voltage dependent calcium channel , t type calcium channel , biology , calcium channel , chemistry , membrane potential , biophysics , signal transduction , biochemistry , receptor , organic chemistry
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. Key points Calcium influx, via voltage‐dependent calcium channels, drives numerous neuronal signalling processes with precision achieved in part by tight coupling between calcium entry and calcium‐dependent effectors. α2δ proteins are important for neurological function and contribute to calcium channel membrane trafficking, although how α2δ proteins influence postsynaptic calcium‐dependent signalling is largely unexplored. Here it is shown that loss of α2δ‐2 proteins disrupts functional calcium coupling to two different postsynaptic calcium‐dependent signals in mouse Purkinje cell neurons, retrograde endocannabinoid signalling and the action potential afterhyperpolarization. The findings provide new insights into the control of calcium coupling as well as new roles for α2δ‐2 proteins in neurons.