Different anesthetic sensitivities of skeletal and cardiac isoforms of the Ca-ATPase

Brad S. Karon, Joseph M. Autry, Yongli Shi, Christine E. Garnett, Giuseppe Inesi, Larry Jones, Howard Kutchai, David D. Thomas

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)9301-9307
Number of pages7
JournalBiochemistry
Volume38
Issue number29
DOIs
StatePublished - Jul 20 1999

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Adenosine Triphosphatases
Anesthetics
Protein Isoforms
Sarcoplasmic Reticulum
Halothane
Sf9 Cells
Organelles
Insects
Conformations
Membrane Proteins
Stabilization
Binding Sites
Tissue
Lipids
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Karon, B. S., Autry, J. M., Shi, Y., Garnett, C. E., Inesi, G., Jones, L., ... Thomas, D. D. (1999). Different anesthetic sensitivities of skeletal and cardiac isoforms of the Ca-ATPase. Biochemistry, 38(29), 9301-9307. https://doi.org/10.1021/bi990190u

Different anesthetic sensitivities of skeletal and cardiac isoforms of the Ca-ATPase. / Karon, Brad S.; Autry, Joseph M.; Shi, Yongli; Garnett, Christine E.; Inesi, Giuseppe; Jones, Larry; Kutchai, Howard; Thomas, David D.

In: Biochemistry, Vol. 38, No. 29, 20.07.1999, p. 9301-9307.

Research output: Contribution to journalArticle

Karon, BS, Autry, JM, Shi, Y, Garnett, CE, Inesi, G, Jones, L, Kutchai, H & Thomas, DD 1999, 'Different anesthetic sensitivities of skeletal and cardiac isoforms of the Ca-ATPase', Biochemistry, vol. 38, no. 29, pp. 9301-9307. https://doi.org/10.1021/bi990190u
Karon, Brad S. ; Autry, Joseph M. ; Shi, Yongli ; Garnett, Christine E. ; Inesi, Giuseppe ; Jones, Larry ; Kutchai, Howard ; Thomas, David D. / Different anesthetic sensitivities of skeletal and cardiac isoforms of the Ca-ATPase. In: Biochemistry. 1999 ; Vol. 38, No. 29. pp. 9301-9307.
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