Figure 8.

TTX-induced downregulation of voltage-gated Na ⁺ channels mimics the effects of early withdrawal from amphetamine. A shows a representative burst response to an sEPSC (400 pA) somatic input before (black trace) and during (gray trace, open triangle) infusion of TTX on BS action potential threshold and spike timing latency. The gray open triangle shows the TTX trace in the scatter plot in B. B shows the relationship between the spike threshold and latency during infusion of low concentrations of TTX. A linear fit line shows a positive correlation between threshold and spike latency (R² = 0.99). The holding potentials were similar before (–60.3 ± 0.38 mV) and after TTX (–60.6 ± 0.45 mV). C shows the subthreshold sEPSP response to a 200 pA (left) and 300 pA (right) sEPSC somatic input taken 400 msec apart and 300 msec before the burst trace seen in A. Note the near-threshold amplification only in the 300 pA trace. The subthreshold sEPSCs were injected every 300–400 msec while TTX washed in the recording chamber. The before and after TTX traces shown were 40 sec apart. Under our experimental conditions, TTX (500 nm) reached sufficient concentrations in the recording chamber to eliminate the action potentials between 240 and 300 sec. All TTX time points were taken between 30 and 60 sec from the entry of TTX into the recording chamber. Action potentials in A are truncated.