How Do Volatile Anesthetics Inhibit Ca2+-ATPases?

López, Marı́a M.; Kosk‐Kosicka, Danuta

doi:10.1074/jbc.270.47.28239

Cited by 31 publications

(11 citation statements)

References 56 publications

(64 reference statements)

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“…Various functional effects of VA have been reported for several membrane proteins studied in Vitro; however, the molecular mechanism of anesthetic action on any of them is not known. We have recently established a connection between the in Vitro effects of VA on the activity and changes in spectroscopic properties of an integral plasma membrane protein, Ca 2+ -ATPase (PMCA), that points to VA effects on enzyme conformation (Lopez & Kosk-Kosicka, 1995). The observed correlation is in agreement with VA binding in the protein that interferes with the conformational transition which the enzyme normally undergoes in its catalytic cycle.…”

mentioning

confidence: 79%

“…For technical reasons, the binding could be studied only for the activatory phase of the halothane effect on SERCA1. For PMCA, we have shown that the inhibition correlates well with the elimination of the crucial conformational change induced by Ca 2+ binding in the initial step of the enzymatic cycle (Lopez & Kosk-Kosicka, 1995). As a first approximation, in an attempt to simplify the mathematical treatment, we are considering the inhibition constants for the two enzymes as the dissociation constants for the anestheticprotein interaction.…”

Section: Inhibition Of Ca 2+ -Atpase Activity By Halothane Inmentioning

confidence: 99%

“…The observed correlation is in agreement with VA binding in the protein that interferes with the conformational transition which the enzyme normally undergoes in its catalytic cycle. We have proposed that such binding is responsible for the observed inhibition of enzymatic function (Lopez & Kosk-Kosicka, 1995). Recently, using direct labeling with [ 14 C]halothane of SERCA1, we have demonstrated that the anesthetic binds saturably to the sarcoplasmic reticulum (SR) membranes, and 40-50% label incorporates directly in the Ca 2+ -ATPase protein (Kosk-Kosicka et al, 1997).…”

mentioning

confidence: 99%

“…When studied in Vitro at clinical halothane concentrations, SERCA1 is activated and then inhibited at higher concentrations. PMCA is more sensitive than SERCA1 to the inhibitory effects of various VA (Lopez & Kosk-Kosicka, 1995). For comparison, we have included a different (nonvolatile, intravenous) general anesthetic, propofol, recently introduced in clinical anesthesia.…”

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confidence: 99%

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Entropy-Driven Interactions of Anesthetics with Membrane Proteins

López

Kosk‐Kosicka

1997

Biochemistry

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Thermodynamic analysis of anesthetic effects on Ca2+-ATPase activity was performed to evaluate the feasibility of anesthetic binding and gain insight into the molecular events underlying the anesthetic-enzyme interactions. The Ca2+-ATPases, integral membrane proteins vital in cellular Ca2+ regulation, are suitable models for investigation of the mechanism of anesthetic action on membrane proteins that are targeted by the anesthetics. Ca2+-ATPase of plasma membrane, PMCA, and SERCA1 in the intracellular sarcoplasmic reticulum membrane were used to study two general anesthetics: halothane, a halogenated two-carbon alkane; and propofol, an intravenous, strongly lipophilic-substituted phenol. Interactions of both anesthetics result in a negative Gibbs free energy change, which in both enzymes is more favorable for the more lipophilic propofol than halothane. Temperature dependence (more negative change in Gibbs free energy at increased temperature) is in agreement with predominantly nonpolar interactions. The interactions are entropy-driven, characterized by positive enthalpy which is overcompensated by positive entropy changes. This is in contrast to the reported in literature enthalpy-driven anesthetic binding to soluble proteins. The possible contributions to the observed positive entropy change are discussed including displacement of ordered water molecules by anesthetic binding in nonpolar cavities in the membrane proteins and subtle structural rearrangements.

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confidence: 79%

Section: Inhibition Of Ca 2+ -Atpase Activity By Halothane Inmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Entropy-Driven Interactions of Anesthetics with Membrane Proteins

López

Kosk‐Kosicka

1997

Biochemistry

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“…In addition, the xenon induced anesthesia is related to the inhibition of the calcium ATPase pump on the cell membrane of synapses [13], which results from a conformational change when xenon binds to nonpolar sites inside the protein [14], and the non-specific interactions between the xenon and the lipid membrane [15]. …”

Section: Mechanisms Underlying Bioeffects Of Xenonmentioning

confidence: 99%

Xenon preconditioning: molecular mechanisms and biological effects

Liu

Chen³

et al. 2013

Medical Gas Research

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Xenon is one of noble gases and has been recognized as an anesthetic for more than 50 years. Xenon possesses many of the characteristics of an ideal anesthetic, but it is not widely applied in clinical practice mainly because of its high cost. In recent years, numerous studies have demonstrated that xenon as an anesthetic can exert neuroprotective and cardioprotective effects in different models. Moreover, xenon has been applied in the preconditioning, and the neuroprotective and cardioprotective effects of xenon preconditioning have been investigated in a lot of studies in which some mechanisms related to these protections are proposed. In this review, we summarized these mechanisms and the biological effects of xenon preconditioning.

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Investigation of plant-derived phenolic compounds as plasma membrane Ca2+-ATPase inhibitors with potential cardiovascular activity

Roufogalis

Tran

et al. 1999

Drug Dev. Res.

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How Do Volatile Anesthetics Inhibit Ca2+-ATPases?

Cited by 31 publications

References 56 publications

Entropy-Driven Interactions of Anesthetics with Membrane Proteins

Entropy-Driven Interactions of Anesthetics with Membrane Proteins

Xenon preconditioning: molecular mechanisms and biological effects

Investigation of plant-derived phenolic compounds as plasma membrane Ca2+-ATPase inhibitors with potential cardiovascular activity

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