Physiological calcium-binding proteins and calcium-selective ion channels (CaBPs and Ca2+ channels)

This broad category encompasses a diverse array of proteins responsible for the regulation and transduction of calcium (Ca2+) signals, which serve as a primary second messenger in nearly all eukaryotic cells [1]. Calcium-selective ion channels, including voltage-gated calcium channels (VGCCs) and store-operated channels like ORAI1, facilitate the controlled entry of Ca2+ into the cytoplasm from the extracellular environment or internal stores such as the endoplasmic reticulum [2]. Once intracellular Ca2+ levels rise, physiological calcium-binding proteins (CaBPs) like calmodulin, troponin C, and parvalbumin act as either sensors that trigger downstream biological effects or buffers that shape the spatio-temporal dynamics of the calcium signal [3]. These proteins are fundamental to critical processes such as cardiac and skeletal muscle contraction, neurotransmitter release in the central nervous system, and the regulation of gene transcription [4]. Due to their central role in physiology, they are major therapeutic targets; for instance, calcium channel blockers are a cornerstone in treating hypertension and arrhythmias, while gabapentinoids target specific calcium channel subunits to manage neuropathic pain and epilepsy [5]. Dysregulation of these systems is linked to a wide spectrum of pathologies, including heart failure, neurodegeneration, and malignant hyperthermia [6]. (Citations: [1] UniProt Calcium-binding; [2] IUPHAR/BPS Guide to Pharmacology; [3] PubMed PMC3073433; [4] StatPearls Calcium Channel Blockers; [5] NIH/NCBI Gene Database; [6] Nature Reviews Drug Discovery).

Other names

Calcium-binding proteinsCalcium-selective channelsCalcium signaling proteinsIntracellular calcium buffersVoltage-gated calcium channelsStore-operated calcium channels

Inhibition of calcium ion influx through voltage-gated or ligand-gated channels; modulation of intracellular calcium release from the sarcoplasmic reticulum; buffering of cytosolic calcium concentrations to regulate signaling cascades.