Voltage-dependent calcium channel proteins (VDCCs), also named as voltage-gated calcium channel proteins (VGCCs), are a group of calcium ion channels present in many cell types from muscle cells and neurons to endocrine cells and lymphocytes. They are multimeric transmembrane proteins that consist of a main pore-forming or α1 subunit and auxiliary subunits, α2δ, and β subunits. And α1 subunit plays a key role in maintaining the normal channel functions. VDCCs mediate the influx of calcium ions into excitable and nonexcitable cells in response to membrane potential changes. And the influx of calcium ions is involved in the many physiological processes, including synaptic transmission, muscle contraction, and gene expression. Additionally, the dysfunctions of VDCCs may lead to the disorder of calcium homeostasis and induce multiple serious human pathophysiological processes, such as muscle disorders, epilepsy, mood disorders, acute and chronic pain, cardiovascular disease, and cancer.
Here shows part of VDCCs in humans including two pore calcium channel protein 1 (TPCN1) and two pore calcium channel protein 2 (TPCN2). TPCN2 possesses four homologous domains with 6 transmembrane segments (S1 to S6) each. While TPCN1 only has two homologous domains containing segments S1 to S6 each. The two pore calcium channel proteins are found in lysosomes and involved in the mediation of calcium release from lysosomal stores in an NAADP-dependent manner.
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