Ca2signalkedjor

Ca2signalkedjor refer to cellular signaling pathways that rely on changes in intracellular calcium ion (Ca2+) concentrations to relay information and regulate cellular processes. As ubiquitous second messengers, Ca2+ signals control activities ranging from rapid responses to long-term changes in gene expression.

Ca2+ signals arise from Ca2+ entry across the plasma membrane through voltage-gated calcium channels, ligand-gated channels, and store-operated channels, as well as from release of Ca2+ from intracellular stores in the endoplasmic/sarcoplasmic reticulum via IP3 receptors and ryanodine receptors. IP3 is produced by phospholipase C after activation of G protein–coupled receptors or receptor tyrosine kinases. Local high Ca2+ concentrations can create microdomains and waves, enabling precise spatial and temporal control.

Ca2+ binds to effector proteins, most notably calmodulin, which activates a variety of kinases such as CaMKII and CaMKIV, phosphatases such as calcineurin, and other enzymes. This signaling network regulates transcription factors like NFAT and CREB, metabolic enzymes, vesicular trafficking, and ion channel activity. DAG and Ca2+ together can activate protein kinase C, linking Ca2+ signaling to lipid signaling pathways.

Termination and shaping of Ca2+ signals involve extrusion by plasma membrane Ca2+-ATPases and Na+/Ca2+ exchangers, resequestration into the ER by SERCA pumps, mitochondria taking up Ca2+ via the MCU, and buffering by Ca2+-binding proteins. The combination of amplitude, duration, and frequency of Ca2+ transients underpins encoding of information.

Ca2+ signaling is essential for muscle contraction, synaptic transmission, hormone release, and gene regulation. Dysregulation is linked to cardiac arrhythmias, neurodegenerative disorders, and other diseases, highlighting the importance of precise control of Ca2+ dynamics.