The effects of oxaliplatin, an anticancer drug, on potassium channels of the peripheral myelinated nerve fibres of the adult rat

A possible link of oxaliplatin‐induced neuropathy with potassium channel deficit

“…They studied these channels because their activation time constant is of a similar order as the duration of oxaliplatin-induced after-activity that persists over several tens of milliseconds after each action potential. 13,21,25 Our study has shown that the channels with a much shorter time constant (like that of fast potassium channels) could be at the root of long-lasting processes. The strongly restricted volume of periaxonal space makes the processes along the internodal membrane considerably different from what is classically considered.…”

“…Benoit et al 23 also reported oxaliplatin-induced negative shifts in the voltage dependence of sodium and potassium channel activation and of sodium channel inactivation in voltage-clamp experiments. Adelsberger et al 21 found no effect of oxaliplatin on potassium channels, which is in contrast to studies reporting an effect of oxaliplatin on potassium channels in frog 23 and adult rat 25 peripheral myelinated axons (MA). Dimitrov 26 proposed a model predicting that the very thin periaxonal space (about a few nanometers) made the low density of internodal sodium channels sufficient for generation of active internodal processes.…”

“…These peripheral myelinated fibers have the thinnest myelin. If the oxaliplatin manages to reach the fiber membrane through myelin, as proposed by Kagiava et al, 25 then the Ad fibers (and thus the fast potassium channels in them) should be the most affected among all MA. Therefore, any minor sensory stimulus able to produce a single sAP (the cold sensation, among others) could induce a much stronger repetitive response in the corresponding MA.…”

“…This implies changes in the shape of the sodium current in rat preparations. Kagiava et al 25 found no effect on the amplitude and depolarization phase of the compound action potential and concluded that sodium channels were not affected by oxaliplatin in their sciatic nerve preparation. Benoit et al 23 also reported oxaliplatin-induced negative shifts in the voltage dependence of sodium and potassium channel activation and of sodium channel inactivation in voltage-clamp experiments.…”

An association between transient hypokalemia and severe acute oxaliplatin-related toxicity predominantly in women

“…Recently reported ex-vivo work suggests that oxaliplatin may interfere with voltage-gated potassium channels [8]. We hypothesize that axonal membrane hyperpolarization [9,10] may account for the observed hypokalemia, with potassium ion channel activation resulting in an intracellular infl ux of potassium.…”