Kalciumsensing

Kalciumsensing refers to the cellular and physiological processes that detect and respond to changes in calcium ion (Ca2+) concentrations. It encompasses extracellular sensing of Ca2+ as well as intracellular and organellar calcium signaling, all of which are essential for maintaining calcium homeostasis and coordinating diverse cellular functions.

Extracellular calcium sensing is primarily mediated by the calcium-sensing receptor (CaSR), a class C G protein–coupled receptor expressed in the parathyroid gland, kidneys, bones, and other tissues. Binding of Ca2+ to CaSR modulates parathyroid hormone (PTH) secretion and influences renal reabsorption of calcium and phosphate, as well as vitamin D metabolism. Mutations in CaSR or pharmacologic modulators can disrupt calcium balance, leading to conditions such as familial hypocalciuric hypercalcemia or autosomal dominant hypocalcemia. Calcimimetics and calcilytics target CaSR to adjust PTH release in various disorders.

Intracellular calcium sensing involves calcium-binding proteins that translate Ca2+ signals into cellular responses. Calmodulin and other EF-hand proteins sense cytosolic Ca2+ rises and regulate enzymes, transcription factors, and metabolic pathways. Calcium also enters cells through channels whose activity is tightly regulated by Ca2+, while organelles such as the endoplasmic reticulum store Ca2+ and use sensors like STIM1 to detect store depletion and trigger store-operated calcium entry via ORAI channels.

Physiologically, calcium sensing governs muscle contraction, neurotransmitter release, hormone secretion, enzyme activity, bone remodeling, and renal function. Malfunctions in calcium sensing contribute to metabolic bone disease, electrolyte disturbances, and broader endocrine and neuromuscular disorders.