Hyperglycaemic hypoxia alters after‐potential and fast K+ conductance of rat axons by cytoplasmic acidification.

The effects of hyperglycaemic hypoxia (a condition possibly involved in the pathogenesis of diabetic neuropathy) on the depolarizing after-potential and the potassium conductance of myelinated rat spinal root axons were investigated using electrophysiological recordings from intact spinal roots and from excised, inside-out axonal membrane patches. 2. Isolated spinal roots were exposed to hypoxia in solutions containing normal or high glucose concentrations. The depolarizing after-potential of compound action potentials was only enhanced in spinal roots exposed to hyperglycaemic (25 mM D-glucose) hypoxia. A maximal effect was seen in bathing solutions with low buffering power. 3. The depolarizing after-potential was also enhanced by cytoplasmic acidification after replacement of 10-30 mM chloride in the bathing solution by propionate. 4. Multi-channel current recordings from excised, inside-out axonal membrane patches were used to study the effects of cytoplasmic acidification on voltage-dependent K+ conductances with fast (F channels) and intermediate (I channels) kinetics of deactivation. 5. F channels were blocked by small changes in cytoplasmic pH (50% inhibition at pH 6.9). I channels were much less sensitive to intra-axonal acidification. 6. In conclusion, our data show that hyperglycaemic hypoxia enhances the depolarizing after-potential in peripheral rat axons. The underlying mechanism seems to be an inhibition of a fast, voltage-dependent axonal K+ conductance by cytoplasmic acidification. This alteration in membrane conductance may contribute to positive symptoms in diabetic neuropathy.