Ion Trafficking through T-type Ca²⁺ Channels : A Way to Look at Channel Gating Position

Voltage-gated Ca²⁺ channels play a key role in controlling Ca²⁺ entry during cell depolarization. At least 10 genes encode the main (α₁) subunits of voltage-gated Ca²⁺ channels, which have been grouped into two main classes: the high voltage–activated (HVA) and the low voltage–activated (LVA) channels. HVA channels are primarily involved in muscle contraction, synaptic transmission, and hormone secretion, while LVA channels are associated with action potential generation and repetitive electrical activity. Structurally speaking, the Ca²⁺ channel α₁ subunits forming the pore share strong similarities with other voltage-gated ion channels, in particular with Na⁺-conducting pores (Hille, 2001). Each α₁ subunit has four domains (I–IV) linked together in a single polypeptide chain and each domain contains six putative transmembrane segments (S1–S6), plus a loop (P) that dips partially into the pore to, presumably, form the...