Plasma membrane calcium-transporting ATPase 3 (PMCA3)

Plasma membrane calcium-transporting ATPase 3 (PMCA3), encoded by the ATP2B3 gene, is a P-type ATPase enzyme and ion transporter found in the plasma membrane of diverse human cells, particularly neurons. It functions by actively extruding calcium ions (\(\mathrm{Ca}^{2+}\)) from the cytosol to the extracellular space against steep concentration gradients, utilizing ATP hydrolysis for energy. This activity is essential for maintaining low resting intracellular calcium concentrations, enabling finely tuned calcium signaling, synaptic transmission, and muscle function. At least four PMCA isoforms exist in mammals, with tissue-specific and developmentally regulated splicing implying precise physiological adaptation. Mutations or dysfunction in PMCA3/ATP2B3 have been linked to hereditary spinocerebellar ataxia and may contribute to other neurodegenerative and excitability disorders, highlighting its therapeutic relevance. PMCA3 is also a pharmacological target for specific inhaled anesthetics (e.g., desflurane, halothane), which can inhibit its activity, resulting in altered calcium dynamics. Major safety concerns for therapeutics impacting this protein center on neuro- and cardiotoxicity related to disrupted calcium homeostasis.

Other names

PMCA3ATP2B3Plasma membrane calcium ATPase isoform 3Plasma membrane calcium pump isoform 3CFAP39Cilia and flagella associated protein 39CLA2OPCASCAX1

Inhibition of calcium transport activity; Modulation of intracellular calcium signaling via ATPase inhibition; Potential alteration in synaptic function or muscle/neuronal excitability