Heterogeneous halothane binding in the SR Ca<sup>2+</sup>‐ATPase

Kosk‐Kosicka, Danuta; Fomitcheva, Ioulia; López, Marı́a M.; Eckenhoff, Roderic G.

doi:10.1016/s0014-5793(96)01526-8

Cited by 18 publications

(16 citation statements)

References 31 publications

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“…It is possible that several molecules of CLT bind to hydrophobic "cavities" in the Ca 2ϩ -ATPase, and to accommodate the intruding CLT, the ATPase undergoes structural rearrangement that results in loss of its enzymatic and ion transport functions. Such a mechanism has been suggested for the inhibitory action of anesthetics on Ca 2ϩ -ATPases (28), and direct anesthetic binding to the SR Ca 2ϩ -ATPase has been demonstrated recently (29). It is noteworthy that CLT inhibited the energy transducing and ion transporting functions of the Ca 2ϩ -ATPase at the same concentration range.…”

Section: Discussionmentioning

confidence: 77%

Clotrimazole, an Antimycotic Drug, Inhibits the Sarcoplasmic Reticulum Calcium Pump and Contractile Function in Heart Muscle

Šnajdrová

Narayanan

1998

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 77%

Clotrimazole, an Antimycotic Drug, Inhibits the Sarcoplasmic Reticulum Calcium Pump and Contractile Function in Heart Muscle

Šnajdrová

Narayanan

1998

Journal of Biological Chemistry

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“…The Ca 2+ -ATPase constitutes only 0.1% or less of the total erythrocyte membrane protein; nonetheless, it can be purified to homogeneity by calmodulin affinity chromatography [18,24]. We first probed the purified Ca 2+ -ATPase on Western blots with anti-PHB IgG [20].…”

Section: Resultsmentioning

confidence: 99%

Novel components and enzymatic activities of the human erythrocyte plasma membrane calcium pump

Reusch¹,

Huang²,

Kosk‐Kosicka³

1997

FEBS Letters

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“…In PMCA, the Ca 2ϩ -ATPase activity, the Ca 2ϩ -dependent conformational change that the protein undergoes upon Ca 2ϩ binding in the initial step of the enzymatic cycle, and the intrinsic Trp fluorescence (11 Trp residues) are affected by volatile anesthetics in a dosedependent manner (Lopez and Kosk-Kosicka, 1995). We have also shown for the first time that the effects of halothane on the Ca 2ϩ -ATPase of the intracellular sarcoplasmic reticulum (SERCA1) are the result of direct binding of the anesthetic to that protein (Kosk-Kosicka et al, 1997). In the present study we are investigating the properties and the environment of the halothane-binding sites in the PMCA by fluorescence spectroscopy.…”

Section: Introductionmentioning

confidence: 92%

Spectroscopic Analysis of Halothane Binding to the Plasma Membrane Ca2+-ATPase

López

Kosk‐Kosicka

1998

Biophysical Journal

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The intrinsic tryptophan (Trp) fluorescence of the plasma membrane Ca2+-ATPase (PMCA) is significantly quenched by halothane, a volatile anesthetic common in clinical practice. It has been proposed that halothane inhibition of the Ca2+-ATPase activity results from conformational changes following anesthetic binding in the enzyme. We have investigated whether the observed quenching reflects halothane binding to PMCA. We have shown that the quenching is dose dependent and saturable and can be fitted to a binding curve with an equilibrium constant K(Hal) = 2.1 mM, a concentration at which the anesthetic approximately half-maximally inhibits the Ca2+-ATPase activity. The relatively low sensitivity of halothane quenching of Trp fluorescence to the concentration of phosphatidylcholine and detergent in the PMCA preparation concurs with the quenching resulting from anesthetic binding in the PMCA molecule. Analysis of the Trp fluorescence quenching by acrylamide indicates that the Trp residues are not considerably exposed to the solvent (Stern-Volmer quenching constant of 2.9 M(-1)) and do not differ significantly in their accessibility to halothane. Other volatile anesthetics, diethyl ether and diisopropyl ether, reduce the quenching caused by halothane in a dose-dependent manner, suggesting halothane displacement from its binding site(s). These observations indicate that halothane quenching of intrinsic Trp fluorescence of PMCA results from anesthetic binding to the protein. The analysis, used as a complementary approach, provides new information to the still rudimentary understanding of the process of anesthetic interaction with membrane proteins.

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Heterogeneous halothane binding in the SR Ca²⁺‐ATPase

Cited by 18 publications

References 31 publications

Clotrimazole, an Antimycotic Drug, Inhibits the Sarcoplasmic Reticulum Calcium Pump and Contractile Function in Heart Muscle

Clotrimazole, an Antimycotic Drug, Inhibits the Sarcoplasmic Reticulum Calcium Pump and Contractile Function in Heart Muscle

Novel components and enzymatic activities of the human erythrocyte plasma membrane calcium pump

Spectroscopic Analysis of Halothane Binding to the Plasma Membrane Ca2+-ATPase

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Heterogeneous halothane binding in the SR Ca2+‐ATPase

Cited by 18 publications

References 31 publications

Clotrimazole, an Antimycotic Drug, Inhibits the Sarcoplasmic Reticulum Calcium Pump and Contractile Function in Heart Muscle

Clotrimazole, an Antimycotic Drug, Inhibits the Sarcoplasmic Reticulum Calcium Pump and Contractile Function in Heart Muscle

Novel components and enzymatic activities of the human erythrocyte plasma membrane calcium pump

Spectroscopic Analysis of Halothane Binding to the Plasma Membrane Ca2+-ATPase

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Heterogeneous halothane binding in the SR Ca²⁺‐ATPase