Fig. 4.

Oxaliplatin and cooling enhance I_NaR and I_NaP TTX-s Na_v currents in large-diameter DRG neurons. (A) Representative current traces in response to voltage commands to −75, −45, −25, and −5 mV (Upper lane) from large-diameter (40.6 ± 4.5 μm, n = 25) DRG neurons from wild-type (WT, Left) and Scn8a^med/med mice (Right) at 30 °C and 22 °C after incubation with oxaliplatin (30 μM; ∼90 min). (B) Peak I_NaR as a function of voltage for recordings at 30 °C [open symbols: WT n = 5;5 and Scn8a^med/med: n = 4;6 (DMSO; oxaliplatin)] and 22 °C (filled symbols, WT: n = 10;11, Scn8a^med/med: n = 6;8) from DRG neurons incubated with vehicle (1% vol/vol DMSO) or oxaliplatin. (C) Representative voltage command (Upper) and current (Lower) traces indicating the period over which the I_NaP component was determined (400–475 ms). (D) I_NaP shown as a function of voltage for recordings at 30 °C (open symbols, WT n = 5;5 and Scn8a^med/med n = 8;11 for DMSO; oxaliplatin) and 22 °C (filled symbols, WT: n = 10;11, Scn8a^med/med: n = 6;8) from large-diameter DRG neurons (WT Left, Scn8a^med/med Right) after incubation with vehicle (black) or oxaliplatin (orange). (E) Corrected I_NaR amplitude as a function of voltage for recordings at 30 °C (open) and 22 °C (filled) from large-diameter DRG neurons (WT Left, Scn8a^med/med Right) after incubation with vehicle (black) or oxaliplatin (orange). I_NaR was corrected for each individual trace by subtracting the I_NaP component (D) from the peak I_NaR (B). Mice ranging in age from P14–25 were used. (*P < 0.05, **P < 0.01).