Neuronal Voltage-Gated Calcium Channels: Structure, Function, and Dysfunction

Abstract

Voltage-gated calcium channels are the primary mediators of depolarization-induced calcium entry into neurons. There is great diversity of calcium channel subtypes due to multiple genes that encode calcium channel α1 subunits, coassembly with a variety of ancillary calcium channel subunits, and alternative splicing. This allows these channels to fulfill highly specialized roles in specific neuronal subtypes and at particular subcellular loci. While calcium channels are of critical importance to brain function, their inappropriate expression or dysfunction gives rise to a variety of neurological disorders, including, pain, epilepsy, migraine, and ataxia. This Review discusses salient aspects of voltage-gated calcium channel function, physiology, and pathophysiology.

Autism throughout genetics: Perusal of the implication of ion channels

“…L‐type channels are predominantly expressed in the heart and brain. They are localized at dendrites and cell bodies of mature neurons and regulate neuronal excitability and Ca 2+ ‐dependent signaling cascades involving cAMP‐binding protein (CREB) and myocyte enhancer factor 2 (MEF2; Krey & Dolmetsch, 2007; Simms & Zamponi, 2014). CACNA1C plays a key role in the development and functionality of the central nervous system by modulating gamma‐aminobutyric acid (GABA) transmission and influencing neuronal firing.…”

“…T‐type voltage‐gated Ca 2+ channels are known to play a key role in the cerebral cortex and in the thalamus (Simms & Zamponi, 2014). Four heterozygous missense variations in CACNA1H gene, encoding the Ca v 3.2 subunit of T‐type channels, were found associated with decreased channel activity in six of 461 autistic patients.…”

Characterization of Cav1.4 Complexes (α11.4, β2, and α2δ4) in HEK293T Cells and in the Retina

“…Neuronal Ca v channels are multiprotein complexes composed of a major pore-forming ␣ 1 subunit, and two auxiliary subunits, ␤ and ␣ 2 ␦, which not only regulate the functional properties of the ␣ 1 subunit but also are important for the proper trafficking of the ␣ 1 subunit to the plasma membrane and protection of the ␣ 1 subunit from proteosomal degradation (reviewed in Refs. [1][2][3][4]. Ten different genes encode the Ca v ␣ 1 subunits, whereas the ␤ and ␣ 2 ␦ subunits are encoded by four genes each (5,6).…”

“…Sections were incubated overnight at 4°C in a mix of diluted primary antibodies: mouse anti-CaBP4 (1:100) plus rabbit anti-Ca v 1.4 (1:1000), rat anti-␤ 2 (1:25) plus rabbit antiCa v 1.4 (1:1000), or rat anti-␣ 2 ␦ 4 (1:25) plus rabbit anti-Cav1. 4 (1:1000). A mix of Alexa Fluor 555-conjugated goat anti-mouse IgG or Alexa Fluor 555-conjugated goat anti-rat IgG and Alexa 488-conjugated goat anti-rabbit IgG was reacted with the sections for 1 h at room temperature.…”

Morphological and functional diversity of first-order somatosensory neurons

“…In the absence of functional voltage-gated sodium channels, Ca V channels are capable of regenerative depolarization (Chen et al 1987). There are multiple isoforms of Ca V channels (reviewed by Simms and Zamponi 2014), and sensory neurons express several types. One interesting example of calcium channels directly controlling the firing rate was demonstrated for the Ca V regulatory subunit α2δ-1 (Margas et al 2016).…”