Calcium Channels, Synaptic Plasticity, and Neuropsychiatric Disease

Neuron. 2018 May 2;98(3):466-481. doi: 10.1016/j.neuron.2018.03.017.

Abstract

Voltage-gated calcium channels couple depolarization of the cell-surface membrane to entry of calcium, which triggers secretion, contraction, neurotransmission, gene expression, and other physiological responses. They are encoded by ten genes, which generate three voltage-gated calcium channel subfamilies: CaV1; CaV2; and CaV3. At synapses, CaV2 channels form large signaling complexes in the presynaptic nerve terminal, which are responsible for the calcium entry that triggers neurotransmitter release and short-term presynaptic plasticity. CaV1 channels form signaling complexes in postsynaptic dendrites and dendritic spines, where their calcium entry induces long-term potentiation. These calcium channels are the targets of mutations and polymorphisms that alter their function and/or regulation and cause neuropsychiatric diseases, including migraine headache, cerebellar ataxia, autism, schizophrenia, bipolar disorder, and depression. This article reviews the molecular properties of calcium channels, considers their multiple roles in synaptic plasticity, and discusses their potential involvement in this wide range of neuropsychiatric diseases.

Keywords: autism; calcium channel; migraine; periodic paralysis; psychiatric disease; synapse; synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Calcium Channels / chemistry
  • Calcium Channels / physiology*
  • Calcium Signaling / physiology*
  • Humans
  • Mental Disorders / diagnosis
  • Mental Disorders / genetics
  • Mental Disorders / physiopathology*
  • Mutation / physiology*
  • Neuronal Plasticity / physiology*
  • Protein Structure, Secondary

Substances

  • Calcium Channels