Inhibiting a Pump Within a Pump

Science's STKE  04 Mar 2003:
Vol. 2003, Issue 172, pp. tw92-TW92
DOI: 10.1126/stke.2003.172.tw92

Heart failure affects nearly 5 million people in the United States. Most inherited forms of heart failure have been linked to defects in cardiac contractile proteins. Schmitt et al. show that heart failure can be initiated by disturbances of calcium metabolism in heart muscle cells. Humans with an inherited form of congestive heart failure were found to have a mutation in phospholamban (PLN), a protein that inhibits the cardiac sarcoplasmic reticulum Ca2+-ATPase (SERCA2a). Subsequent experiments revealed that the mutant PLN causes constitutive inhibition of SERCA2a, leading to alterations in Ca2+ kinetics.

J. P. Schmitt, M. Kamisago, M. Asahi, G. H. Li, F. Ahmad, U. Mende, E. G. Kranias, D. H. MacLennan, J. G. Seidman, C. E. Seidman, Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science 299, 1410-1413 (2003). [Abstract] [Full Text]