Chronic intermittent hypoxia increases excitability and synaptic excitation of protrudor and retractor hypoglossal motoneurones

Autor(es)

da Silva, Melina P. ^[1] ; Magalhaes, Karolyne S. ^[1] ; de Souza, Daniel P. ^[1] ; Moraes, Davi J. A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PHYSIOLOGY-LONDON; v. 599, n. 6 FEB 2021.
• Citações Web of Science: 0

Resumo

Key points Dysfunctions in the hypoglossal control of tongue extrinsic muscles are implicated in obstructive sleep apnoea (OSA) syndrome. Chronic intermittent hypoxia (CIH), an important feature of OSA syndrome, produces deleterious effects on the motor control of oropharyngeal resistance, but whether the hypoglossal motoneurones innervating the tongue extrinsic muscles are affected by CIH is unknown. We show that CIH enhanced the respiratory-related activity of rat hypoglossal nerve innervating the protrudor and retractor tongue extrinsic muscles. Intracellular recordings revealed increases in respiratory-related firing frequency and synaptic excitation of inspiratory protrudor and retractor hypoglossal motoneurones after CIH. CIH also increased their intrinsic excitability, depolarised resting membrane potential and reduced K+-dominated leak conductance. CIH affected the breathing-related synaptic control and intrinsic electrophysiological properties of protrudor and retractor hypoglossal motoneurones to optimise the neural control of oropharyngeal function. Inspiratory-related tongue movements and oropharyngeal motor actions are controlled mainly by the protrudor and retractor extrinsic tongue muscles, which are innervated by the hypoglossal motoneurones. Chronic intermittent hypoxia (CIH), an important feature of obstructive sleep apnoea syndrome, produces detrimental effects on the contractile function of the tongue extrinsic muscles and the medullary inspiratory network of rodents. However, the impact of the CIH on the electrophysiological properties of protrudor and retractor hypoglossal motoneurones has not been described before. Using nerves and intracellular recordings in in situ preparation of rats (5 weeks old), we tested the hypothesis that CIH (FiO(2) of 0.06, SaO(2) 74%, during 30-40 s, every 9 min, 8 h/day for 10 days) increases the intrinsic excitability of protrudor and retractor motoneurones from the hypoglossal motor nucleus of rats. Recordings of hypoglossal nerve, before its bifurcation to innervate the tongue protrudor and retractor muscles, revealed that CIH enhances its pre-inspiratory, simultaneously with the presence of active expiration, and inspiratory activities. These changes were mediated by increases in the respiratory-related firing frequency and synaptic excitation of inspiratory protrudor and retractor hypoglossal motoneurones. Besides, CIH increases their intrinsic excitability and depolarises resting membrane potential by reducing a K+-dominated leak conductance. In conclusion, CIH enhances the respiratory-related neural control of oropharyngeal function of rats by increasing the synaptic excitation, intrinsic excitability, and reducing leak conductance in both protrudor and retractor hypoglossal motoneurones. We propose that these network and cellular changes are important to optimise the oropharyngeal resistance in conditions related to intermittent hypoxia. (AU)

• Processo FAPESP: 18/15957-2 - Modulação astrocítica dos neurônios bulbares envolvidos com a geração e controle das atividades simpática e respiratória de roedores submetidos à hipóxia
• Beneficiário: Benedito Honorio Machado
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/11863-6 - Transmissão sináptica e propriedades eletrofisiológicas dos motoneurônios brônquicos do núcleo motor dorsal do vago de ratos
• Beneficiário: Davi José de Almeida Moraes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/24060-9 - Contribuição do Grupo Respiratório parafacial nas respostas inspiratórias, expiratórias e cardiovasculares de ratos à estimulação de fibras aferentes musculares
• Beneficiário: Karolyne Silva Magalhães
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/07027-5 - Participação dos astrócitos na modulação da excitabilidade de neurônios magnocelulares do núcleo supraóptico mediante alterações da osmolalidade plasmática
• Beneficiário: Melina Pires da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores