Ca2activated

Ca2+-activated refers to proteins and processes that increase their activity in response to binding of intracellular calcium ions (Ca2+). Calcium acts as a versatile second messenger; transient rises in cytosolic Ca2+ originate from extracellular influx or release from internal stores and trigger conformational changes or complex assembly in target proteins.

Examples include calcium-activated potassium channels (BK, SK, IK) that open in response to Ca2+ to shape neuronal excitability and smooth muscle tone; calcium-activated chloride channels such as TMEM16A that participate in secretion and epithelial transport; and calcium-activated enzymes such as calmodulin-dependent kinases (CaMKs) and calcineurin that regulate phosphorylation and signaling networks. Calcium-binding proteins like troponin C in muscle transduce Ca2+ signals to actin-myosin contraction, while synaptotagmin serves as a Ca2+ sensor for rapid neurotransmitter release. Other Ca2+-activated proteins include calpains, which perform regulated proteolysis, and certain phospholipases (e.g., cPLA2) involved in membrane remodeling and inflammatory signaling.

Mechanistically, many Ca2+-activated proteins rely on calcium-binding domains, notably EF-hand motifs. Calmodulin, a ubiquitous Ca2+ sensor, binds Ca2+ and activates targets directly or via intermediary kinases and phosphatases; Ca2+ influx through voltage-gated calcium channels, NMDA receptors, or IP3 receptors provides the signal that couples external stimuli to cellular responses.

Ca2+-activated processes are fundamental to muscle contraction, synaptic transmission, gene expression, and plasticity. Precise regulation of these pathways is essential for normal physiology, and dysregulation can contribute to neurodegenerative disease, cardiac arrhythmias, and ischemic injury.