Activation of medullary α2-adrenoceptors in vitro does not disinhibit laryngeal motoneurons:failure to explain the laryngogenic apnea in vivo induced by α2-adrenoceptors agonists

【作者】 闫先侠； 葛登云； 郭玉红； 陈咏华； 王继江；

【机构】 复旦大学基础医学院生理与病理生理学系；

【摘要】 The preganglionic recurrent laryngeal motoneurons(PRLMs)dominate the neural control of almost all the intrinsic laryngeal muscles.These neurons receive noradrenergic projection,and systemic administration ofα2-adrenoceptor(α2-AR)agonists reportedly causes augmented expiratory activity of the recurrent laryngeal nerve,glottis closure and laryngogenic apnea,however the central mechanisms remain unknown.The present study aimed to test the hypothesis that activation of medullaryα2-ARs causes disinhibition of the PRLMs,and via which causes glottis closure and laryngogenic apnea.Putative PRLMs were retrogradely labeled from bilateral recurrent laryngeal nerves of newborn rats and functionally identified as inspiratory-activated and inspiratory-inhibited PRLMs(IA-PRLMs and Ⅱ-PRLMs)in rhythmically firing brainstem slices.The effects of dexmedetomidine,a highly selectiveα2-AR agonist,were examined using the patch-clamp techniques.The results show that both types of the PRLMs receive predominant GABAergic,less glycinergic and very scarce glutamatergic synaptic inputs.Under voltage clamp,dexmedetomidine caused slight but significant decreases of the frequency of glycinergic inhibitory postsynaptic currents(IPSCs)in Ⅱ-PRLMs,but had little effect on the GABAergic IPSCs and the glutamatergic excitatory postsynaptic currents(EPSCs)in either the frequency or amplitude.Under current clamp,dexmedetomidine failed to depolarize the membrane potential and reduced the firing rate in either type of the PRLMs.These results demonstrate that dexmedetomidine only has a minor inhibitory effect selectively on the glycinergic synaptic inputs of the PRLMs,which is not enough to alter the firing of these neurons.Our results indicate that the glottis closure and larygogenic apnea induced by systemic administration ofα2-AR agonists in vivo are not mediated solely by activation ofα2-ARs at the levels of the PRLMs and their synaptic inputs.更多还原

【Abstract】 The preganglionic recurrent laryngeal motoneurons(PRLMs) dominate the neural control of almost all the intrinsic laryngeal muscles.These neurons receive noradrenergic projection,and systemic administration of α2-adrenoceptor(α2-AR) agonists reportedly causes augmented expiratory activity of the recurrent laryngeal nerve,glottis closure and laryngogenic apnea,however the central mechanisms remain unknown.The present study aimed to test the hypothesis that activation of medullary α2-ARs causes disinhibition of the PRLMs,and via which causes glottis closure and laryngogenic apnea.Putative PRLMs were retrogradely labeled from bilateral recurrent laryngeal nerves of newborn rats and functionally identified as inspiratory-activated and inspiratory-inhibited PRLMs(IA-PRLMs and Ⅱ-PRLMs) in rhythmically firing brainstem slices.The effects of dexmedetomidine,a highly selective α2-AR agonist,were examined using the patch-clamp techniques.The results show that both types of the PRLMs receive predominant GABAergic,less glycinergic and very scarce glutamatergic synaptic inputs.Under voltage clamp,dexmedetomidine caused slight but significant decreases of the frequency of glycinergic inhibitory postsynaptic currents(IPSCs) in Ⅱ-PRLMs,but had little effect on the GABAergic IPSCs and the glutamatergic excitatory postsynaptic currents(EPSCs) in either the frequency or amplitude.Under current clamp,dexmedetomidine failed to depolarize the membrane potential and reduced the firing rate in either type of the PRLMs.These results demonstrate that dexmedetomidine only has a minor inhibitory effect selectively on the glycinergic synaptic inputs of the PRLMs,which is not enough to alter the firing of these neurons.Our results indicate that the glottis closure and larygogenic apnea induced by systemic administration of α2-AR agonists in vivo are not mediated solely by activation of α2-ARs at the levels of the PRLMs and their synaptic inputs.更多还原