Anesthetics Have Different Effects on the Electrocorticographic Spectra of Wild-type and Mitochondrial Mutant Mice. (October 2018)

• Record Type: Journal Article
• Authors: Carspecken, Charles William; Chanprasert, Sirisak; Kalume, Franck; Sedensky, Margaret M.; Morgan, Philip G.
• Is Part Of: Anesthesiology. Volume 129:Number 4(2018)
• Publication Date: 2018-10
• Subjects: Anesthesiology -- Periodicals; Anesthetics -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1097/ALN.0000000000002368
• Languages: English
• ISSNs: 0003-3022

Abstract

Editor's Perspective: What We Already Know about This Topic: In genetically engineered mice that lack a specific protein ( Ndufs4 ) in complex I of the electron transport chain in mitochondria of glutamatergic neurons, sensitivity to volatile anesthetics is markedly increased; by contrast, these mice are resistant to the anesthetic action of ketamine Whether the differing sensitivity to volatile anesthetics and to ketamine in the Ndufs4 knockout mice is reflected in cortical electrical activity, measured by electrocorticography, was determined What This Article Tells Us That Is New: While isoflurane and halothane suppressed electrocor ticography in all frequency bands in control mice, in Ndufs4 knockout mice, both agents decreased power in the higher frequency bands (beta, gamma), whereas activity in the lower bands (delta, theta, and alpha) was maintained Ketamine also decreased power in the Ndufs4 knockout mice in the beta and gamma frequency bands only The data indicate that in Ndufs4 knockout mice, an energetic state in glutamatergic neurons impacts anesthetic sensitivity, and this sensitivity is reflected in cortical electrical activity Background: Knockout of the mitochondrial protein Ndufs4 ( Ndufs4[KO] ) in mice causes hypersensitivity to volatile anesthetics but resistance to ketamine. The authors hypothesized that electrocorticographic changes underlying the responses of Ndufs4(KO ) to volatile anesthetics and to ketamine would be similar in mutant and control mice. Methods: Electrocorticographic recordings at equipotent volatile anesthetic concentrations were compared between genotypes. In separate studies, control and cell type-specific Ndufs4(KO ) mice were anesthetized with intraperitoneal ketamine to determine their ED50s. Results: Ndufs4 (KO ) did not differ from controls in baseline electrocorticography (N = 5). Compared to baseline, controls exposed to isoflurane (EC50) lost power (expressed as mean baseline [µV 2 /Hz]; mean isoflurane [µV 2 /Hz]) in delta (2.45; 0.50), theta (1.41; 0.16), alpha (0.23; 0.05), beta (0.066; 0.016), and gamma (0.020; 0.005) frequency bands (N = 5). Compared to baseline, at their isoflurane EC50, Ndufs4(KO ) maintained power in delta (1.08; 1.38), theta (0.36; 0.26), and alpha (0.09; 0.069) frequency bands but decreased in beta (0.041; 0.023) and gamma (0.020; 0.0068) frequency bands (N = 5). Similar results were seen for both genotypes in halothane. Vesicular glutamate transporter 2 (VGLUT2 )-specific Ndufs4(KO ) mice were markedly resistant to ketamine (ED50; 125 mg/kg) compared to control mice (ED50; 75 mg/kg; N = 6). At their respective ED95s for ketamine, mutant (N = 5) electrocorticography spectra showed a decrease in power in the beta (0.040; 0.020) and gamma (0.035; 0.015) frequency bands not seen in controls (N = 7). Conclusions: Significant differences exist between the electrocorticographies of mutant and control mice at equipotent doses for volatile anesthetics and ketamine. The energetic state specifically of excitatory neurons determines the behavioral response to ketamine. Abstract : While isoflurane and halothane suppressed electrocorticography in all frequency bands in control mice, in Ndufs4 knockout mice, both agents decreased power in the higher frequency bands (beta, gamma), whereas activity in the lower bands (delta, theta, and alpha) was maintained. Ketamine also decreased power in the Ndufs4 knockout mice in the beta and gamma frequency bands only. The data indicate that in Ndufs4 knockout mice, an energetic state in glutamatergic neurons impacts anesthetic sensitivity, and this sensitivity is reflected in cortical electrical activity.Supplemental Digital Content is available in the text.