Different Anesthetic Sensitivities of Skeletal and Cardiac Isoforms of the Ca-ATPase† Export

@article{citeulike:5337685, abstract = {PMID: 10413504 We have previously shown that low levels of the volatile anesthetic halothane activate the Ca-ATPase in skeletal sarcoplasmic reticulum (SR), but inhibit the Ca-ATPase in cardiac SR. In this study, we ask whether the differential inhibition is due to (a) the presence of the regulatory protein phospholamban in cardiac SR, (b) different lipid environments in skeletal and cardiac SR, or (c) the different Ca-ATPase isoforms present in the two tissues. By expressing skeletal (SERCA 1) and cardiac (SERCA 2a) isoforms of the Ca-ATPase in Sf21 insect cell organelles, we found that differential anesthetic effects in skeletal and cardiac SR are due to differential sensitivities of the SERCA 1 and SERCA 2a isoforms to anesthetics. Low levels of halothane inhibit the SERCA 2a isoform of the Ca-ATPase, and have little effect on the SERCA 1 isoform. The biochemical mechanism of halothane inhibition involves stabilization of E2 conformations of the Ca-ATPase, suggesting direct anesthetic interaction with the ATPase. This study establishes a biochemical model for the mechanism of action of an anesthetic on a membrane protein, and should lead to the identification of anesthetic binding sites on the SERCA 1 and SERCA 2a isoforms of the Ca-ATPase.}, author = {Karon, Brad S. and Autry, Joseph M. and Shi, Yongli and Garnett, Christine E. and Inesi, Giuseppe and Jones, Larry R. and Kutchai, Howard and Thomas, David D.}, citeulike-article-id = {5337685}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/bi990190u}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/bi990190u}, day = {1}, doi = {10.1021/bi990190u}, journal = {Biochemistry}, keywords = {anaesthetic, atpase, calcium, cardiac, muscle, pump, reticulum, sarcoendoplasmic, serca1, serca2, skeletal}, month = {July}, number = {29}, pages = {9301--9307}, posted-at = {2009-08-03 09:08:31}, priority = {2}, title = {Different Anesthetic Sensitivities of Skeletal and Cardiac Isoforms of the Ca-ATPase{\dag}}, url = {http://dx.doi.org/10.1021/bi990190u}, volume = {38}, year = {1999} }

TY - JOUR ID - citeulike:5337685 L3 - citeulike-article-id:5337685 N2 - PMID: 10413504 We have previously shown that low levels of the volatile anesthetic halothane activate the Ca-ATPase in skeletal sarcoplasmic reticulum (SR), but inhibit the Ca-ATPase in cardiac SR. In this study, we ask whether the differential inhibition is due to (a) the presence of the regulatory protein phospholamban in cardiac SR, (b) different lipid environments in skeletal and cardiac SR, or (c) the different Ca-ATPase isoforms present in the two tissues. By expressing skeletal (SERCA 1) and cardiac (SERCA 2a) isoforms of the Ca-ATPase in Sf21 insect cell organelles, we found that differential anesthetic effects in skeletal and cardiac SR are due to differential sensitivities of the SERCA 1 and SERCA 2a isoforms to anesthetics. Low levels of halothane inhibit the SERCA 2a isoform of the Ca-ATPase, and have little effect on the SERCA 1 isoform. The biochemical mechanism of halothane inhibition involves stabilization of E2 conformations of the Ca-ATPase, suggesting direct anesthetic interaction with the ATPase. This study establishes a biochemical model for the mechanism of action of an anesthetic on a membrane protein, and should lead to the identification of anesthetic binding sites on the SERCA 1 and SERCA 2a isoforms of the Ca-ATPase. IS - 29 JF - Biochemistry EP - 9307 TI - Different Anesthetic Sensitivities of Skeletal and Cardiac Isoforms of the Ca-ATPase† VL - 38 SP - 9301 KW - anaesthetic KW - atpase KW - calcium KW - cardiac KW - muscle KW - pump KW - reticulum KW - sarcoendoplasmic KW - serca1 KW - serca2 KW - skeletal AU - Karon, Brad AU - Autry, Joseph AU - Shi, Yongli AU - Garnett, Christine AU - Inesi, Giuseppe AU - Jones, Larry AU - Kutchai, Howard AU - Thomas, David PY - 1999/07/01/ UR - http://dx.doi.org/10.1021/bi990190u ER -