Intra-axonal recording from large sensory myelinated axons: demonstration of impaired membrane conductances in early experimental diabetes.
OBJECTIVE
Diabetic neuropathy is accompanied by a range of positive (paresthaesia, dysesthaesia, pain) and negative (hypesthaesia, anesthaesia) neurological symptoms suggesting widespread alterations in axonal excitability. The nature and the mechanisms underlying these alterations in axonal excitability are not well understood. The aim of this study was to examine the extent of changes in membrane properties of an identified neuronal structure-the large myelinated sensory axons in early experimental diabetes in rats.


METHODS
Intra-axonal microelectrode recordings from large sensory myelinated axons from the isolated sural nerve in short-term streptozotocin-induced diabetic rats were used to study membrane properties using standard current-clamp technique.


RESULTS
In addition to decreased conduction velocity we found several differences in physiological properties of sensory axons from diabetic rats: decreased resting membrane potential, decreased single action potential amplitude associated with slower rate of rise and decrease in inward rectification associated with slight alteration in outwardly rectifying conductances indicating impaired potassium conductances.


CONCLUSIONS
These results extend previous indirect evidence that potassium and sodium ionic conductances, most notably the inward rectifier (IR, I(h)), are altered in large sensory axons of diabetic rats. The depression of IR could underly clinical neurological findings in diabetic patients.
Kriz
Jasna
J
Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade (ex-Drummond), Montréal, Quebec H3G 1Y6, Canada.
Padjen
Ante L
AL
D000200:Action Potentials; D000818:Animals; D001369:Axons; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004553:Electric Conductivity; D004594:Electrophysiology; D066298:In Vitro Techniques; D007425:Intracellular Membranes; D008297:Male; D008564:Membrane Potentials; D009413:Nerve Fibers, Myelinated; D009431:Neural Conduction; D009475:Neurons, Afferent; D051381:Rats; D017207:Rats, Sprague-Dawley; D013497:Sural Nerve / Q000503:physiopathology*; D013997:Time Factors