Ulyanovsk Medico-biological Journal

PHYSIOLOGY

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DOI 10.34014/2227-1848-2019-1-68-75

RESPIRATORY RESPONSE ON THE ACTIVATION OF GABAА- AND GABAВ-RECEPTORS OF A PARAFACIAL RESPIRATORY GROUP BY SPECIFIC AGONISTS

 

T.E. Kovaleva, O.A. Vedyasova

Samara National Research University named after S.P. Korolev, Samara, Russia

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The purpose of the paper is to conduct comparative analysis of GABAА and GABAВ receptors of the parafacial respiratory group (pFRG) in central mechanisms of respiratory regulation in adult rats.

Materials and Methods. The authors studied the reactions of external respiration and diaphragmatic muscle on microinjections of muscimol and baclofen solutions (10-6 M, 200 nl) in the region of pFGR on rats, anesthetized with urethane. Injections were administered through a glass microcannula according to stereotactic coordinates. A spirogram and electromyogram (EMG) of the diaphragm were recorded in the initial state and within 60 minutes after microinjection of the abovementioned agonists of GABAА and GABAВ receptors.

Results. Microinjections of muscimol, the agonist of GABAA receptors, in pFGR had an inhibitory effect on respiration. The inhibitory effect was characterized by a short latent period. Minute lung ventilation decreased in rats due to changes in tidal volume and respiratory rate, while the inspiratory and expiratory time increased. On the EMG of the diaphragm, the oscillation amplitude decreased, while the duration of inspiratory bursts and inter-burst intervals increased. Microinjections of baclofen solution, GABAВ agonist receptor, in pFGR also caused respiratory depression, but with a longer latency period. In that case, a decrease in pulmonary ventilation was provided by a decrease in tidal volume in combination with inspiration lengthening. Changes in the breathing pattern corresponded to a decrease in the oscillation amplitude and an increase in the duration of inspiratory bursts on the EMG of the diaphragm.

Conclusions. The role of pFGR in the respiratory regulation is mediated by ionotropic GABAА- and metabotropic GABAB-receptors. GABAA-receptors in the pFHR area contribute to expiration-inspiration regulation, while GABAB-receptors are predominantly involved in inspiratory activity modulation.

Keywords: parafacial respiratory group, GABAA-receptors, GABAB-receptors, muscimol, baclofen, external respiration, electromyogram of the diaphragm.

 

References

  1. Feldman J.L., Del Negro C.A., Gray P.A. Understanding the rhythm of breathing: So near, yet so far. Ann. Rev. Physiol. 2013; 75: 423–452.
  2. Onimaru H., Homma I. A novel functional neuron group for respiratory rhythm generation in the ventral medulla. J. Neurosci. 2003; 23 (4): 1478–1486.
  3. Pisanski A., Pagliardini S. The parafacial respiratory group and the control of active expiration. Respir. Physiol. Neurobiol. 2018. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29933053 (accessed: 10.12.2018). DOI: 10.1016/j.resp.2018.06.010.
  4. Abbott S.B., Stornetta R.L., Coates M.B., Guyenet P.G. Phox2b-expressing neurons of the parafacial region regulate breathing rate, inspiration, and expiration in conscious rats. J. Neurosci. 2011; 31 (45): 16410–16422.
  5. Silva J.N., Tanabe F.M., Moreira T.S., Takakura A.C. Neuroanatomical and physiological evidence that the retrotrapezoid nucleus/parafacial region regulates expiration in adult rats. Respir. Physiol. Neurobiol. 2016; 227: 9–22.
  6. Onimaru H., Ikeda K., Kawakami K. Phox2b, RTN/pFRG neurons and respiratory rhythmogenesis. Respir. Physiol. Neurobiol. 2009; 168 (1–2): 13–18.
  7. De Britto A.A., Moraes D.J. Non-chemosensitive parafacial neurons simultaneously regulate active expiration and airway patency under hypercapnia in rats. J. Physiol. 2017; 595 (6): 2043–2064.
  8. Boutin R.C., Alsahafi Z., Pagliardini S. Cholinergic modulation of the parafacial respiratory group. J. Physiol. 2017; 595 (4): 1377–1392.
  9. Huckstepp R.T., Cardoza K.P., Henderson L.E., Feldman J.L. Role of parafacial nuclei in control of breathing in adult rats. J. Neurosci. 2015; 35 (3): 1052–1067.
  10. Vedyasova O.A., Kovaleva T.E. Role of GABAA receptors of parafacial respiratory group in control of respiration in rats. Bull. Exp. Biol. Med. 2018; 165 (6): 711–714.
  11. Fortuna M.G., West G.H., Stornetta R.L., Guyenet P.G. Betzinger expiratory-augmenting neurons and the parafacial respiratory group. J. Neurosci. 2008; 28 (10): 2506–2515.
  12. Pagliardini S., Janczewski W.A., Tan W., Dickson C.T., Deisseroth K., Feldman J.L. Active expiration induced by excitation of ventral medulla of adult anesthetized rats. J. Neurosci. 2011; 31 (8): 2895–2905.
  13. Li P., Janczewski W.A., Yackle K., Kam K., Pagliardini S., Krasnow M.A., Feldman J.L. The peptidegic control circuit for sighing. Nature. 2016; 530 (7590): 293–297.
  14. Misgeld U., Bijak M., Jarolimek W. A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system. Prog. Neurobiol. 1995; 46 (4): 423–462.
  15. Belan P.V., Kostyuk P.G. Glutamate-receptor-induced modulation of GABAergic synaptic transmission in the hippocampus. Pflugers Arch. 2002; 444 (1): 26–37.
  16. Cherubini E., Conti F. Generating diversity at GABAergic synapses. Trends Neurosci. 2001; 24 (3): 155–162.
  17. Bochorishvili G., Stornetta R.L., Coates M.B., Guyenet P.G. Pre-Betzinger complex receives glutamatergic innervation from galaninergic and other retrotrapezoid nucleus neurons. J. Comp. Neurol. 2012; 520 (5): 1047–1061.
  18. Smith J.C., Abdala A.P., Rybak I.A., Paton J.F. Structural and functional architecture of respiratory networks in the mammalian brainstem. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 2009; 364 (1529): 2577–2587.

 

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DOI 10.34014/2227-1848-2019-1-68-75

УДК 612.28

 

РЕАКЦИИ ДЫХАНИЯ НА АКТИВАЦИЮ ГАМКА- И ГАМКВ-РЕЦЕПТОРОВ ПАРАФАЦИАЛЬНОЙ РЕСПИРАТОРНОЙ ГРУППЫ СПЕЦИФИЧЕСКИМИ АГОНИСТАМИ

Т.Е. Ковалева, О.А. Ведясова

ФГАОУ ВО «Самарский национальный исследовательский университет им. академика С.П. Королева», г. Самара, Россия

e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Цель. Сравнительный анализ роли ГАМКА- и ГАМКВ-рецепторов парафациальной респираторной группы (пФРГ) в центральных механизмах регуляции дыхания у взрослых крыс.

Материалы и методы. На наркотизированных уретаном крысах исследовали реакции внешнего дыхания и диафрагмальной мышцы на микроинъекции в область пФРГ растворов мусцимола и баклофена (10-6 М, 200 нл). Инъекции осуществляли через стеклянную микроканюлю по стереотаксическим координатам. Регистрировали спирограмму и электромиограмму (ЭМГ) диафрагмы в исходном состоянии и в течение 60 мин после микроинъекции указанных агонистов ГАМКА- и ГАМКВ-рецепторов.

Результаты. Микроинъекции в пФРГ агониста ГАМКА-рецепторов мусцимола оказывали на дыхание тормозное действие, которое развивалось с коротким латентным периодом. У крыс снижалась минутная вентиляция легких за счет изменений дыхательного объема и частоты дыхания, увеличивалось время вдоха и выдоха. На ЭМГ диафрагмы уменьшалась амплитуда осцилляций, увеличивалась длительность инспираторных залпов и межзалповых интервалов. Микроинъекции в пФРГ раствора агониста ГАМКВ-рецепторов баклофена также вызывали угнетение дыхания, но с более длительным латентным периодом. Снижение легочной вентиляции в данном случае обеспечивалось уменьшением дыхательного объема в сочетании с удлинением вдоха. Изменениям паттерна дыхания соответствовало уменьшение амплитуды осцилляций и увеличение длительности инспираторных залпов на ЭМГ диафрагмы.

Выводы. Участие пФРГ в регуляции дыхания опосредуется ионотропными ГАМКА- и метаботропными ГАМКВ-рецепторами. ГАМКА-рецепторы в области пФРГ вносят вклад в регуляцию экспирации и инспирации, тогда как ГАМКВ-рецепторы преимущественно участвуют в модуляции инспираторной активности.

Ключевые слова: парафациальная респираторная группа, ГАМКА-рецепторы, ГАМКВ-рецепторы, мусцимол, баклофен, внешнее дыхание, электромиограмма диафрагмы.

 

Литература

  1. Feldman J.L., Del Negro C.A., Gray P.A. Understanding the rhythm of breathing: So near, yet so far. Ann. Rev. Physiol. 2013; 75: 423–452.
  2. Onimaru H., Homma I. A novel functional neuron group for respiratory rhythm generation in the ventral medulla. J. Neurosci. 2003; 23 (4): 1478–1486.
  3. Pisanski A., Pagliardini S. The parafacial respiratory group and the control of active expiration. Respir. Physiol. Neurobiol. 2018. URL: https://www.ncbi.nlm.nih.gov/pubmed/29933053 (дата обращения: 10.12.2018). DOI: 10.1016/j.resp.2018.06.010.
  4. Abbott S.B., Stornetta R.L., Coates M.B., Guyenet P.G. Phox2b-expressing neurons of the parafacial region regulate breathing rate, inspiration, and expiration in conscious rats. J. Neurosci. 2011; 31 (45): 16410–16422.
  5. Silva J.N., Tanabe F.M., Moreira T.S., Takakura A.C. Neuroanatomical and physiological evidence that the retrotrapezoid nucleus/parafacial region regulates expiration in adult rats. Respir. Physiol. Neurobiol. 2016; 227: 9–22.
  6. Onimaru H., Ikeda K., Kawakami K. Phox2b, RTN/pFRG neurons and respiratory rhythmogenesis. Respir. Physiol. Neurobiol. 2009; 168 (1–2): 13–18.
  7. De Britto A.A., Moraes D.J. Non-chemosensitive parafacial neurons simultaneously regulate active expiration and airway patency under hypercapnia in rats. J. Physiol. 2017; 595 (6): 2043–2064.
  8. Boutin R.C., Alsahafi Z., Pagliardini S. Cholinergic modulation of the parafacial respiratory group. J. Physiol. 2017; 595 (4): 1377–1392.
  9. Huckstepp R.T., Cardoza K.P., Henderson L.E., Feldman J.L. Role of parafacial nuclei in control of breathing in adult rats. J. Neurosci. 2015; 35 (3): 1052–1067.
  10. Vedyasova O.A., Kovaleva T.E. Role of GABAA receptors of parafacial respiratory group in control of respiration in rats. Bull. Exp. Biol. Med. 2018; 165 (6): 711–714.
  11. Fortuna M.G., West G.H., Stornetta R.L., Guyenet P.G. Betzinger expiratory-augmenting neurons and the parafacial respiratory group. J. Neurosci. 2008; 28 (10): 2506–2515.
  12. Pagliardini S., Janczewski W.A., Tan W., Dickson C.T., Deisseroth K., Feldman J.L. Active expiration induced by excitation of ventral medulla of adult anesthetized rats. J. Neurosci. 2011; 31 (8): 2895–2905.
  13. Li P., Janczewski W.A., Yackle K., Kam K., Pagliardini S., Krasnow M.A., Feldman J.L. The peptidergic control circuit for sighing. Nature. 2016; 530 (7590): 293–297.
  14. Misgeld U., Bijak M., Jarolimek W. A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system. Prog. Neurobiol. 1995; 46 (4): 423–462.
  15. Belan P.V., Kostyuk P.G. Glutamate-receptor-induced modulation of GABAergic synaptic transmission in the hippocampus. Pflugers Arch. 2002; 444 (1): 26–37.
  16. Cherubini E., Conti F. Generating diversity at GABAergic synapses. Trends Neurosci. 2001; 24 (3): 155–162.
  17. Bochorishvili G., Stornetta R.L., Coates M.B., Guyenet P.G. Pre-Betzinger complex receives glutamatergic innervation from galaninergic and other retrotrapezoid nucleus neurons. J. Comp. Neurol. 2012; 520 (5): 1047–1061.
  18. Smith J.C., Abdala A.P., Rybak I.A., Paton J.F. Structural and functional architecture of respiratory networks in the mammalian brainstem. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 2009; 364 (1529): 2577–2587.