Figure 1.
Effect of 7,8-dihydroxyflavone on neuromuscular transmission in diaphragm muscle of TrkBF616A knockin mice. A. Representative tracing of force evoked by repetitive stimulation of a diaphragm-phrenic nerve preparation. Maximal isometric twitch force was obtained by direct muscle stimulation (first peak). The phrenic nerve was then stimulated at 40-Hz. Direct muscle stimulation was superimposed every 15 s via plate electrodes. Repetitive stimulation results in muscle fatigue, which is evident as a decrease in force. The contribution of neuromuscular transmission failure to muscle fatigue can then be calculated from the difference in force elicited by nerve and muscle stimulation (see text for details). B. Time course of neuromuscular transmission failure for TrkBF616A diaphragm muscle. Vehicle treatment (open circles) shows increasing neuromuscular transmission failure over time, which is consistent with previous results in the rat.1,16–19 Treatment with 7,8-dihydroxyflavone (closed circles) reduced neuromuscular transmission failure, reflecting enhanced neuromuscular transmission. The effect of 7,8-dihydroxyflavone was completely blocked by 1NMPP1 treatment (open triangles), indicating a specific effect on TrkB receptor kinase activity, since TrkBF616A knockin mice harbor a mutation that renders TrkB susceptible to inhibition by 1NMPP1.12 *, different from vehicle-treated group at same time-point; #, different from 1NMPP1- and 7,8-dihydroxyflavone-treated group at same time-point (p<0.05).