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.
OBJECTIVE: To investigate the effects of hyperglycemia on axonal excitability and potassium conductance in humandiabetic 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 diabeticpatients. The effects of hyperglycemia on these indices were analyzed. RESULTS: Among diabeticpatients, 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 humandiabetic neuropathy, whereas multiple factors can affect especially internodal properties.
Authors: Andreas C Themistocleous; Alexander G Kristensen; Roma Sola; Sandra S Gylfadottir; Kristine Bennedsgaard; Mustapha Itani; Thomas Krøigård; Lise Ventzel; Søren H Sindrup; Troels S Jensen; Hugh Bostock; Jordi Serra; Nanna B Finnerup; Hatice Tankisi; David L H Bennett Journal: Ann Neurol Date: 2022-03-07 Impact factor: 11.274
Authors: Angelika Bierhaus; Thomas Fleming; Stoyan Stoyanov; Andreas Leffler; Alexandru Babes; Cristian Neacsu; Susanne K Sauer; Mirjam Eberhardt; Martina Schnölzer; Felix Lasitschka; Felix Lasischka; Winfried L Neuhuber; Tatjana I Kichko; Ilze Konrade; Ralf Elvert; Walter Mier; Valdis Pirags; Ivan K Lukic; Michael Morcos; Thomas Dehmer; Naila Rabbani; Paul J Thornalley; Diane Edelstein; Carla Nau; Josephine Forbes; Per M Humpert; Markus Schwaninger; Dan Ziegler; David M Stern; Mark E Cooper; Uwe Haberkorn; Michael Brownlee; Peter W Reeh; Peter P Nawroth Journal: Nat Med Date: 2012-06 Impact factor: 53.440
Authors: Natalie C G Kwai; Ria Arnold; Chathupa Wickremaarachchi; Cindy S-Y Lin; Ann M Poynten; Matthew C Kiernan; Arun V Krishnan Journal: Diabetes Care Date: 2013-02-12 Impact factor: 19.112