Abnormal Axonal Inward Rectification in Diabetic Neuropathy

An abnormal axonal membrane conductance might contribute to human diabetic neuropathy. To test this idea, we have compared the threshold changes produced by long-lasting (100-200 ms) de- and hyperpolarizing currents applied to median motor and sensory axons at the wrist in 63 diabetic patients with those from 50 normal controls and 27 amyotrophic lateral sclerosis (ALS) patients. Averages of the threshold electrotonus plots for motor and sensory axons of diabetic patients showed more subexcitability during, and slower recovery following, the application of hyperpolarizing currents. Such alterations have been previously found in isolated rat nerves after inhibition of axonal inward rectification by means of cesium ions. The abnormalities in diabetics were positively correlated with the age of patients and the presence of neuropathy. Threshold electrotonus seen in diabetes differed strongly from the effects of acute ischemia and were unlike changes recorded in ALS. The data indicate that an abnormal inward rectification of peripheral axons is associated with diabetic neuropathy. A better understanding of the neurobiology of this conductance might provide information about the pathophysiology of this disease.