RESUMEN
Mechanisms that could mitigate the effects of hypoxia on neuronal signaling are incompletely understood. We show that axonal performance of a locust visual interneuron varied depending on oxygen availability. To induce hypoxia, tracheae supplying the thoracic nervous system were surgically lesioned and action potentials in the axon of the descending contralateral movement detector (DCMD) neuron passing through this region were monitored extracellularly. The conduction velocity and fidelity of action potentials decreased throughout a 45-min experiment in hypoxic preparations, whereas conduction reliability remained constant when the tracheae were left intact. The reduction in conduction velocity was exacerbated for action potentials firing at high instantaneous frequencies. Bath application of octopamine mitigated the loss of conduction velocity and fidelity. Action potential conduction was more vulnerable in portions of the axon passing through the mesothoracic ganglion than in the connectives between ganglia, indicating that hypoxic modulation of the extracellular environment of the neuropil has an important role to play. In intact locusts, octopamine and its antagonist, epinastine, had effects on the entry to, and recovery from, anoxic coma consistent with octopamine increasing overall neural performance during hypoxia. These effects could have functional relevance for the animal during periods of environmental or activity-induced hypoxia.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Hipoxia/patología , Fibras Nerviosas Amielínicas/efectos de los fármacos , Conducción Nerviosa/efectos de los fármacos , Octopamina/farmacología , Potenciales de Acción/efectos de los fármacos , Agonistas alfa-Adrenérgicos/uso terapéutico , Animales , Inhibidores Enzimáticos/farmacología , Lateralidad Funcional/efectos de los fármacos , Saltamontes , Oxigenoterapia Hiperbárica/métodos , Masculino , Movimiento/efectos de los fármacos , Fibras Nerviosas Amielínicas/fisiología , Octopamina/uso terapéutico , Técnicas de Placa-Clamp , Estimulación Luminosa , Azida Sódica/farmacología , Nervios Torácicos/patología , Factores de TiempoRESUMEN
Modern approaches to drug discovery have dramatically increased the speed and quantity of compounds that are made and tested for potential potency. The task of collecting, organizing, and assimilating this information is a major bottleneck in the discovery of new drugs. We have developed LeadScope a novel, interactive computer program for visualizing, browsing, and interpreting chemical and biological screening data that can assist pharmaceutical scientists in finding promising drug candidates. The software organizes the chemical data by structural features familiar to medicinal chemists. Graphs are used to summarize the data, and structural classes are highlighted that are statistically correlated with biological activity.