Axonal potassium conductance and glycemic control in human diabetic nerves

Objective To investigate the effects of hyperglycemia on axonal excitability and potassium conductance in human diabetic nerves. Methods Threshold tracking was used to measure excitability indices, which depend on potassium channels (supernormality, late subnormality, threshold electrotonus, and a current/threshold relationship) in median motor axons of 96 diabetic patients. The effects of hyperglycemia on these indices were analyzed. Results Among diabetic patients, higher serum hemoglobin A1c (HbA1c) levels were significantly associated with greater supernormality (P=0.04) and smaller late subnormality (P=0.02), suggestive of reduced nodal/paranodal potassium currents under hyperglycemia. Threshold electrotonus and current/threshold relationships did not correlate with HbA1c levels, but partly related with nerve conduction slowing. Conclusions Hyperglycemia could reduce nodal potassium conductances, possibly due to reduced membranous potassium gradient or suppression of potassium channels. In contrast, internodal potassium conductances may be determined by both metabolic factors and structural changes such as exposure of internodal channels by demyelination. Significance Measurements of the excitability indices could provide new insights into nodal and internodal axonal membrane properties in human diabetic neuropathy, whereas multiple factors can affect especially internodal properties