L-type voltage-dependent calcium channels (LVDCCs)

L-type voltage-dependent calcium channels (LVDCCs) are a class of voltage-gated calcium channels. They have a complex structure composed of five subunits: α1, α2, δ, β, and γ. The α1 subunit is the core functional component containing four homologous domains, each with six transmembrane segments (S1-S6). The S1-S4 segments form the voltage sensing domain, while S5-S6 and the P-loop form the conduction pore and gating apparatus. The α1 subunit has cytosolic N and C termini, with a longer C-terminus. The auxiliary subunits (α2, δ, β, γ) modulate channel function and localization; α2 and δ are extracellular, while β and γ are cytosolic. There are four main subtypes: Cav1.1 (skeletal muscle), Cav1.2 (cardiac and smooth muscle), Cav1.3 (sinoatrial node, various tissues), and Cav1.4 (retinal cells). L-type channels are generally high voltage-activated (except Cav1.3), exhibit slower activation kinetics, rapid deactivation, weak voltage-dependent inactivation, and strong calcium-dependent inactivation. They are highly sensitive to dihydropyridine calcium channel blockers. These channels are essential for excitation-contraction coupling in various muscles, regulation of heart rhythm and development, smooth muscle contraction in blood vessels, aldosterone secretion, and signal transduction during muscle excitation-contraction coupling. The 3D structure, determined by electron cryomicroscopy, shows an asymmetrical heart-shaped and handle-shaped structure, approximately 160 × 220 Å.

Other names

L-type calcium channelsCav1.1Cav1.2Cav1.3Cav1.4

L-type calcium channels are highly sensitive to and blocked by drugs like dihydropyridine calcium channel blockers, which modulate calcium influx.