GABAA Receptors: Involvement in the Formation of Respiratory Reactions to Hypoxic Stimulation under Conditions of Mitochondrial Dysfunction
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In experiments on Wistar rats, the role of the state of GABAA receptors in the formation of respiratory responses to hypoxic loading was studied under conditions of the norm and experimental mitochondrial dysfunction; the latter was induced by single systemic injections of 3 mg/kg rotenone, a nonselective blocker of complex I in the respiratory chain of the mitochondria. Volume-time parameters of respiration were characterized according to the parameters of respiratory EMG discharges of the diaphragmatic muscle (amplitude, frequency, and integral intensity). Changes in EMG activity of the diaphragm induced by inhalation of a hypoxic gas mixture (12% О2 + 88% N2) were estimated prior to and after injections of the blocker of GABAA and GABAB receptors bicuculline (bicuculline methiodide, 1.0 mg/kg) in control rats and animals with mitochondrial dysfunction. The development of mitochondrial dysfunction was accompanied by suppression of the respiratory reaction to hypoxic loading, which was manifested in a dramatic decrease in the frequency and integral intensity of EMG discharges of the diaphragmatic muscle. These data can be considered an indication of the considerable involvement of GABAA receptors localized at the postsynaptic membranes of peripheral chemoreceptors in the formation of respiratory response to hypoxic stimulation (including the stage of depression of ventilation); this was observed in both control rats and animals with mitochondrial dysfunction. The involvement of a GABA-ergic link in the formation of respiratory activity related to hypoxic stimulation acquires special significance under conditions of experimental mitochondrial dysfunction leading to occlusion of afferent impulsation coming from peripheral chemoreceptors.
KeywordsGABAA receptors hypoxia ventilatory response peripheral chemoreceptors EMG activity of the diaphragm
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- 11.G. E. Bisgard and J. A. Neubauer, “Peripheral and central effects of hypoxia,” in: Lung Biology in Health and Disease, Marcel Dekker, New York (1995), pp. 617-668.Google Scholar
- 12.J. Neubauer, J. E. Melton, and N. H. Edelman, “Modulation of respiration during brain hypoxia,” J. Appl. Physiol., 68, No. 2, 1462-1470 (1990).Google Scholar
- 17.M. Pokorski, E. Kolesnikova, M. Marczak, and K. Budzinska, “Neurotransmitter mechanisms in the enhancement of the hypoxic ventilatory response by antecedent hyperoxia in the anesthetized rat,” J. Physiol. Pharmacol. (Acta Pol.), 56, 433-446 (2005).Google Scholar
- 29.N. G. Man’shina and O. A. Vedyasova, “Comparative analysis of respiratory reactions to microinjections of GAB and penicillin in the Bötzinger’s complex and pre-Bötzinger’s complex in rats,” Vest. SamGU (Nat. Sci. Ser.), 94, Nos. 3/1, 210-218 (2012).Google Scholar