Fig. 7.
Acute application of Nav channel blockers has differential effects on calcium dynamics modified by ACM-hSOD1G93A. A: flow diagram of experiment. ACM-hSOD1G93A was applied on 5–7 DIV spinal cultures for 30 min (as in Fig. 3) to measure calcium transients (ACM − Nav blockers). Thereafter, Nav channel blockers TTX (1 nM), mexiletine (25 nM), spermidine (10 μM), and riluzole (100 nM) were applied to measure calcium transients of the same neurons 7 min later (ACM + Nav blockers); Nav channel blockers were used at the same concentrations as in Fig. 4. B and C: mean fraction of calcium transient frequencies (B) and amplitudes (C) after ACM-hSOD1G93A and drug treatments (ACM + Nav blockers) relative to ACM-hSOD1G93A alone (ACM − Nav blockers). Note that all Nav channel blockers markedly decreased mean frequency (to 20–30%). However, whereas mexiletine, spermidine, and riluzole significantly decreased the mean amplitude of the calcium transients (to 60%), TTX increases this parameter by ∼225%. Values represent means ± SE from 17–19 neurons/condition, analyzed by 1-way ANOVA followed by a Tukey post hoc test. *P < 0.05, ***P < 0.001 relative to 30-min ACM-hSOD1G93A.