延髄呼吸性ニューロン群の中枢性化学刺激に対する応答様式ラット延髄薄切標本でのpre-Bdtzingercomplexニューロンの律動的バーストに及ぼすCO2, pH変化の効果

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  • Responses to Central Chemostimuli of the Medullary Respiratory Neurons : Effects of CO2 and pH Changes on the Rhythmic Bursts of the pre-Botzinger Complex Neurons in Rat Medullary Slice Preparations

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In in vitro rat brainstem-spinal cord preparations, the pre-Botzinger complex （pre-BotC） has been assumed to be the kernel for spontaneous respiratory rhythm generation and to induce inspiratory motor discharges in the hypoglossal nucleus （XII） neurons and the phrenic motoneurons. The present study was undertaken to clarify the following two points: 1） whether or not the pre-BotC neurons within the ventral respiratory group in the medulla exhibit central chemosensitive responses to CO2 and pH changes; and 2） which is the primary chemosensory stimulus, CO2 or pH, if they do indeed exhibit chemosensitivities. The author examined electrophysiologically the responses of the pre-BotC neurons to CO2 and pH changes in transverse medullary slices （?900μm thick） of neonatal rat （1-5 days old）. Synchronized spontaneous respiratory bursts （0.07?0.2 Hz） in the pre-BotC and the XII neurons were recorded simultaneously with extracellular glass microelectrodes. The responses to CO2 and pH were examined in four different groups: Group 1 （10% CO2, pH 7.1; n=9）, Group 2 （10% CO2, pH 7.4; n=5）, Group 3 （5% CO2, pH 7.1; n=8）, and Group 4 （5% CO2, pH 7.7; n=10）. All slices were subjected to various chemical stimuli for 5 minutes. During recordings, slices were continuously superfused （3-4 ml/min） with mock cerebrospinal fluid with elevated extracellular K+ concentration （10 mM） equilibrated with 95% O2-5% CO2 at 26-29℃. The pre-BotC neurons were observed to respond in parallel with the XII neurons to various chemical stimuli. Groups 1 and 3 produced a significant increase （Group 1: 40±9.1%, mean ± SE, Group 3: 53±8.1%） in the burst frequency of pre-BotC neurons about 3 minutes after the onset of stimuli. Group 2, the normal pH range, however, produced no significant effects on the rhythmic bursts of the pre-BotC neurons. Group 4 showed a significant decrease （20±4.2%）. There were no significant changes in the burst duration, intraburst spike frequency and amplitude of the bursts of the pre-BotC neurons in the above conditions. The present data demonstrate that pre-BotC neurons respond to changes of CO2 and/or pH in transverse medullary slices. The extracellular H+ in particular seems to be the primary chemosensory stimulus in determining the burst frequency. These findings suggest that central chemosensitive neuronal components modulating respiratory rhythm are located at the pre-BotC region and the spontaneous rhythmic activity of the pre-BotC neurons reflects eupneic respiratory activity.

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