Drosophila mutants with opposing effects on nerve excitability: genetic and spatial interactions in repetitive firing.

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Abstract
Drosophila mutants were used to study genetic control of membrane excitability. Opposing effects on nerve excitability were demonstrated by physiological interactions in double mutants. Sh adults exhibit leg-shaking behavior when anesthetized. Repetitive nerve firing and prolonged transmitter release are observed at larval neuromuscular junction, and a reduced K conductance has been suggested. The mutation napts, which decreases nerve excitability, most likely by reducing Na conductance, suppresses both behavioral and physiological defects of Sh. Reducing Na conductance with a subcritical dose of tetrodotoxin (TTX) also suppresses repetitive firing and the prolonged transmitter release in Sh. Severing the axon from the terminal or blocking the Ca2+ influx in the presynaptic terminal by Co2+ or 0 Ca2+ saline abolish repetitive firing in Sh. Electrotonic depolarization of the Sh nerve terminal in the presence of a high dose of TTX reveals increased presynaptic Ca2+ influx. Recording simultaneously at 2 different points along the nerve shows the repetitive spikes propagate antidromically from the terminal. Interdependence between axonal and terminal regions in generating repetitive firing and prolonged transmitter release is suggested. Reducing the excitability at either region inhibits the occurrence of these 2 phenomena. The following model is proposed: The Sh nerve terminal is abnormally excitable. The increased presynaptic Ca current initiated by an axonal Na spike serves as a source of depolarization to trigger additional Na spikes, which in turn further depolarize the terminal or help maintain the depolarization. In the double mutant napts interrupts this cycle, presumably by reducing Na conductance in the axon.