title: Hyperglycaemic hypoxia alters after-potential and fast K+ conductance of rat axons by cytoplasmic acidification.
abstract: 1. 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.
authors.affiliation: Department of Physiology, University of Munich, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Schneider
authors.forename: S
authors.initials: S
authors.lastname: Quasthoff
authors.forename: N
authors.initials: N
authors.lastname: Mitrović
authors.forename: P
authors.initials: P
authors.lastname: Grafe
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001639:Bicarbonates / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008839:Microelectrodes; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D001639:Bicarbonates; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D015761:4-Aminopyridine