RESUMO
Glia modulate neuronal activity by releasing transmitters in a process called gliotransmission. The role of this process in controlling the activity of neuronal networks underlying motor behavior is unknown. ATP features prominently in gliotransmission; it also contributes to the homeostatic ventilatory response evoked by low oxygen through mechanisms that likely include excitation of preBötzinger complex (preBötC) neural networks, brainstem centers critical for breathing. We therefore inhibited glial function in rhythmically active inspiratory networks in vitro to determine whether glia contribute to preBötC ATP sensitivity. Glial toxins markedly reduced preBötC responses to ATP, but not other modulators. Furthermore, since preBötC glia responded to ATP with increased intracellular Ca(2+) and glutamate release, we conclude that glia contribute to the ATP sensitivity of preBötC networks, and possibly the hypoxic ventilatory response. Data reveal a role for glia in signal processing within brainstem motor networks that may be relevant to similar networks throughout the neuraxis.
Assuntos
Trifosfato de Adenosina/fisiologia , Inalação/fisiologia , Rede Nervosa/fisiologia , Neuroglia/fisiologia , Periodicidade , Receptores Purinérgicos/fisiologia , Centro Respiratório/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Trifosfato de Adenosina/farmacologia , Animais , Animais Recém-Nascidos , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/fisiologia , Células Cultivadas , Inalação/efeitos dos fármacos , Rede Nervosa/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Agonistas Purinérgicos , Ratos , Ratos Sprague-Dawley , Centro Respiratório/efeitos dos fármacosRESUMO
The nuclear aod-1 gene of Neurospora crassa encodes the alternative oxidase and is induced when the standard cytochrome-mediated respiratory chain of mitochondria is inhibited. To study elements of the pathway responsible for alternative oxidase induction, we generated a series of mutations in the region upstream from the aod-1 structural gene and transformed the constructs into an aod-1 mutant strain. Transformed conidia were plated on media containing antimycin A, which inhibits the cytochrome-mediated electron transport chain so that only cells expressing alternative oxidase will grow. Using this functional in vivo assay, we identified an alternative oxidase induction motif (AIM) that is required for efficient expression of aod-1. The AIM sequence consists of two CGG repeats separated by 7 bp and is similar to sequences known to be bound by members of the Zn(II)2Cys6 binuclear cluster family of transcription factors. The AIM motif appears to be conserved in other species found in the order Sordariales.