Nomenclature and tissue distribution

Voltage-gated calcium channels may be categorized into two groups based on the membrane potential required for activation [2]. The low-voltage-activated channels include those that are activated at potentials from about -40 to -50 mV. The high-voltage-activated channels are activated at more positive potentials of -35 to +15 mV. The nomenclature assigned to these channels has evolved, and the three primary nomenclature systems listed in Table 1 may still be found in the current literature. Calcium channels are most commonly grouped in families by their kinetic and pharma-cologic current characteristics [5,6]. The low-voltage-activated family is responsible for the transient current (T-type). The high-voltage-activated channel families include those responsible for the long-lasting current (L-type), the current found in Purkinje cells (P/Q-type), the neuronal current (N-type), and the residual current (R-type).

Ten specific mammalian calcium channel subtypes have been identified based on the sequence of their membrane pore-forming a1 subunit. As illustrated in Table 1, calcium channels may be individually identified by their a1 subunit, or more commonly using a systematic nomenclature based on a gene subfamily (Cav1-Cav3) and the order of discovery of the a1 subunit (e.g., Cav1.1-Cav 1.4) [7].

The pore-forming a1 subunit alone is sufficient to form a functional calcium channel in the cell membrane [8]. However, high-voltage-activated calcium channels are hetero-oligomeric structures that may contain as many as three additional smaller subunits, labeled a2d (itself a heterodimer), p, and g. These three subunits associate in an auxiliary

Table 1 Nomenclature of voltage-gated calcium channels

Family

Channel

a1 Subunit

Distribution

L-type

Cavi.i

ais

Sketetal muscle

Cavi.2

aie

Cardiac and smooth muscle, endocrine cells, CNS, neuron cell bodies

Cavi.3

a1D

Cochlea, retina, neuroendocrine cells in the pancreas

Cavi.4

aiF

Retina, lymphoid tissue, spinal chord

P/Q-type

Cav2.1

a1A

Neuron presynaptic terminals, heart, brain

N-type

Cav2.2

aiB

Neuron presynaptic terminals

R-type

Cav2.3

aiE

Neuron cell bodies and presynaptic terminals, heart, pituitary

T-type

Cav3.1

aie

Brain, heart

Cav3.2

aiH

Kidney, liver, brain, heart

Cav3.3

aii

Brain

fashion and are believed to modify both the voltage-gating properties of the channel and the trafficking of the channel to the cell surface. Low-voltage-activated (T-type) calcium channels have not been demonstrated to associate with auxiliary subunits in native tissues [9].

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