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Glossary
- EA2=
- episodic ataxia type 2;
- FHM1=
- familial hemiplegic migraine type 1;
- HVA=
- high voltage-activated;
- LVA=
- low voltage-activated;
- PD=
- Parkinson disease;
- SCA6=
- spinocerebellar ataxia type 6;
- SNc=
- substantia nigra pars compacta;
- SW=
- spike-and-wave.
Voltage-gated calcium (Ca2+) channels are a major source of Ca2+ influx and have a critical role in Ca2+ signaling in all cells. The nervous system expresses a number of different types of voltage-gated Ca2+ channels, each with unique cellular and subcellular distributions and specific physiologic functions. Studies in vitro or in knockout mice have provided insight into the function of the different types of voltage-gated Ca2+ channels. L-Type channels regulate neuronal excitability and gene expression; P/Q and N channels trigger neurotransmitter release, and T-type channels support neuronal rhythmic burst firing. Evidence from natural mutants, knockout mice, and human genetic disorders indicate a fundamental role of some voltage-gated Ca2+ channels in a wide variety of neurologic disorders, including seizures, ataxia, and neuropathic pain. There are several excellent reviews on the structural features, regulation, and function of the different types of voltage-gated Ca2+ channels1–5 and their implication in neurologic diseases.6–10 Only few salient concepts are emphasized here.
SUBTYPES AND STRUCTURE OF VOLTAGE-GATED CALCIUM CHANNELS
Classification.
Voltage-gated Ca2+ channels have been classified into 2 major categories on the basis of their threshold of activation by depolarization, high voltage-activated (HVA) channels, and low voltage-activated (LVA) channels (table 1). The HVA channels can be further subdivided, based on pharmacologic and biophysical characteristics, into L-, N-, P/Q-, and R types.1,2
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Table 1 Main features of voltage-gated calcium channels
Structure.
All voltage-gated Ca2+ channels contain a pore-forming α1 subunit that determines their main biophysical and pharmacologic properties. There are 3 major families of α1 subunits—Cav1, Cav2, and Cav3—each consisting of several subtypes (table 1). The Cav1 family encodes L-type channels; the Cav2 family includes 3 different isoforms that encode P/Q- (Cav2.1), N- (Cav2.2), and R- (Cav2.3) …
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- Neuronal voltage-gated calcium channels: Brief overview of their function and clinical implications
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