Neuronal voltage-gated calcium channels

Abstract

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. ### 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 View this table: 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) …