Activation of alpha-2 noradrenergic receptors is critical for the generation of fictive eupnea and fictive gasping inspiratory activities in mammals in vitro

作者：Viemari Jean Charles^*; Garcia Alfredo J III; Doi Atsushi; Ramirez Jan Marino

来源：European Journal of Neuroscience, 2011, 33(12): 2228-2237.

DOI：10.1111/j.1460-9568.2011.07706.x

• A1C1 neurons
• gasping
• norepinephrine
• pacemaker
• respiration

Biogenic amines are not just 'modulators', they are often essential for the execution of behaviors. Here, we explored the role of biogenic amines acting on the pre-Botzinger complex (pre-BotC), an area located in the ventrolateral medulla which is critical for the generation of different forms of breathing. Isolated in transverse slices from mice, this region continues to spontaneously generate rhythmic activities that resemble normal (eupneic) inspiratory activity in normoxia and gasping in hypoxia. We refer to these as 'fictive eupneic' and 'fictive gasping' activity. When exposed to hypoxia, the pre-BotC transitions from a network state relying on calcium-activated nonspecific cation currents (I(CAN)) and persistent sodium currents (I(Nap)) to one that primarily depends on the I(Nap) current. Here we show that in inspiratory neurons I(Nap)-dependent bursting, blocked by riluzole, but not I(CAN)-dependent bursting, required endogenously released norepinephrine acting on alpha2-noradrenergic receptors (alpha 2-NR). At the network level, fictive eupneic activity persisted while fictive gasping ceased following the blockade of alpha 2-NR. Blockade of alpha 2-NR eliminated fictive gasping even in slice preparations as well as in inspiratory island preparations. Blockade of fictive gasping by alpha 2-NR antagonists was prevented by activation of 5-hydroxytryptamine type 2A receptors (5-HT2A). Our data suggest that gasping depends on the converging aminergic activation of 5-HT2AR and alpha 2-NR acting on riluzole-sensitive mechanisms that have been shown to be crucial for gasping.

• 出版日期2011-6