Ca_V1.x Channels (L-type)

Ca_V1.x channels (L-type) are high-voltage activated Ca²⁺ channels that are sensitive to blockade by dihydropyridines. This family has four members, each composed of an α₁, α₂/δ, β and γ subunit.

Ca_V1.1 channels are specific to skeletal muscle where they interact with ryanodine receptors on the sarcoplasmic reticulum and trigger Ca²⁺ influx, Ca²⁺-activated Ca²⁺ release and muscle contraction. Mutations in Ca_V1.1 α₁-subunit have been linked to hypokalemic periodic paralysis.

Ca_V1.2 and 1.3 channels are found in most excitable cells. In the brain, they are located postsynaptically, where they modulate neuronal firing and Ca²⁺-coupled gene transcription. By supporting neuronal plasticity, these channels are critical to processes such as learning and memory, addiction and neural development. As well as being found in the brain, Ca_V1.2 and 1.3 channels are found in the heart. Ca_V1.2 are the predominant subtype in cardiomyocytes, where they trigger contraction, however they are also found in smaller numbers in sinoatrial and atrioventricular node cells. Ca_V1.3 are the predominant subtype in these cells, and Ca_V1.2 and 1.3 channels play roles at different stages of the cardiac action potential. Additionally, Ca_V1.2 and 1.3 channels are found in endocrine cells; Ca_V1.2 control the fast phase of insulin secretion in mouse pancreatic β-cells, while Ca_V1.3 are required for β-cell proliferation and development. Mutations in the Ca_V1.2 α₁-subunit have been linked to various cardiac arrhythmias, as well as neuropsychiatric diseases including autism. Similarly, mutations in Ca_V1.3 α₁-subunit have been linked to autism, and also Parkinson's disease.

Ca_V1.4 channels are mainly restricted to the retina, where they are essential for normal visual function; congenital stationary night blindness has been linked to mutations in Ca_V1.4 channels.

External sources of pharmacological information for Ca_V1.x Channels (L-type) :

• BJP Guide

Ca_v1.x Voltage-gated Calcium Channel Gene Data