Alcoholic neuropathy-associated changes in K+ conductance of primary dorsal root ganglion neurons

Abstract

Aim: Alcohol-induced peripheral neuropathy (AIN) is a prevalent and debilitating condition, yet current knowledge of the molecular mechanisms is limited. In this study, we aimed to analyze the impact of chronic alcohol exposure on macroscopic K⁺ currents in dorsal root ganglion (DRG) neurons, providing insight into potential therapeutic targets for neuropathic pain.

Methods: An AIN model was established in adult male Sprague-Dawley rats by administering 35% ethanol (10 g/kg, twice daily) for 10 weeks. Whole-cell patch-clamp methodology was applied to measure macroscopic outward K⁺ currents in the DRG. Depolarizing voltage steps (−60 to +100 mV, 10 mV increments) were applied to elicit K⁺ currents. Data were analyzed for current–voltage relationships, conductance–voltage curves, and steady-state activation parameters (maximum conductance, half-activation voltage V₁/₂, and slope factor k).

Results: Electrophysiological recordings revealed that peak K⁺ current amplitudes in DRG neurons were significantly reduced in AIN rats (7.6 ± 0.7 nA) compared to controls (10.2 ± 0.7 nA, p < 0.05) at voltages between + 80 and + 100 mV. Maximum K⁺ conductance was also decreased in the AIN group (42.2 ± 3.9) versus controls (56.1 ± 4.1, p < 0.05). Additionally, V₁/₂ shifted leftward in AIN neurons (1.6 ± 1.9 mV) compared to controls (9.4 ± 2.1 mV), and the slope factor (k) modestly changed from 17.7 ± 1.2 to 20.7 ± 1.1.

Conclusion: By elucidating a key ionic mechanism underlying alcohol-induced neuropathy, this study provides a strong foundation for the development of targeted pharmacotherapies aimed at restoring K⁺ channel function for AIN.