Abstract
Cation-transporting P-type ATPases such as Na+,K+-ATPase, gastric H+,K+-ATPase, and sarcoplasmic reticulum Ca2+-ATPase use energy from ATP hydrolysis to establish electrochemical gradients for ions across cellular membranes. These pumps also perform specialized functions. In particular, sarcoplasmic reticulum Ca2+-ATPase is involved in nonshivering thermogenesis. We have identified the first chemical compound, capsaicin, which uncouples ATP hydrolysis from Ca2+ transport through Ca2+-ATPase. Under physiological conditions, uncoupling of sarcoplasmic reticulum Ca2+-ATPase is likely mediated by interaction with sarcolipin, a small protein highly expressed in skeletal muscle. In addition, we have characterized a drug that selectively abolishes K+-dependent activity of the Na+,K+-ATPase, uncoupling Na+- from Na+,K+ exchange. Here we provide basic information on the function and mechanism of P-type pumps. In addition, we review recent developments on the drug-mediated uncoupling of sarcoplasmic reticulum Ca2+-ATPase and Na+,K+-ATPase.
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These studies were supported by a grant from the Novo Nordic Foundation.
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Mahmmoud, Y.A. (2016). Uncoupling of P-Type ATPases. In: Chakraborti, S., Dhalla, N. (eds) Regulation of Membrane Na+-K+ ATPase. Advances in Biochemistry in Health and Disease, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-319-24750-2_13
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