Nodal persistent Na+ currents in human diabetic nerves estimated by the technique of latent addition.
OBJECTIVE
To investigate the effects of hyperglycemia on persistent Na+ currents in human diabetic nerves, eliminating the factors of passive membrane properties as a factor. Previous studies show that strength-duration time constant of a nerve is shortened under hyperglycemia, suggesting reduced axonal persistent Na+ currents. However, the time constant is also affected by changes in passive membrane properties. Latent addition using computerized threshold tracking is a new method that can separately evaluate Na+ currents and passive membrane properties.


METHODS
Latent addition was used to estimate nodal Na+ currents in median motor axons of 83 diabetic patients. Brief hyperpolarizing conditioning current pulses were delivered, and threshold changes at the conditioning-test interval of 0.2 ms were measured as an indicator of nodal persistent Na+ currents. Seventeen patients were examined before and after insulin treatment.


RESULTS
There was an inverse linear relationship between hemoglobin A1c levels and threshold changes at 0.2 ms (P=0.02); the higher hemoglobin A1c levels were associated with smaller threshold changes. After insulin treatment, there was a significant improvement in nerve conduction velocities associated with greater threshold changes at 0.2 ms (P=0.03), suggesting an increase in persistent Na+ currents. The fast component of latent addition, an indicator of passive membrane properties, was not affected by the state of glycemic control.


CONCLUSIONS
Hyperglycemia could suppress nodal persistent Na+ currents, presumably because of reduced trans-axonal Na+ gradient or impaired Na+ channels, and this can be rapidly restored by glycemic control.


CONCLUSIONS
Reduced nodal Na+ currents may partly contribute to the pathophysiology of human diabetic neuropathy.
Department of Neurology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Sonoko
S
Misawa
Satoshi
S
Kuwabara
Kazuaki
K
Kanai
Noriko
N
Tamura
Miho
M
Nakata
Kazue
K
Ogawara
Kazuo
K
Yagui
Takamichi
T
Hattori
D000200:Action Potentials / Q000502:physiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002462:Cell Membrane / Q000502:physiology; D003929:Diabetic Neuropathies / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D004558:Electric Stimulation; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000503:physiopathology; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000378:metabolism / Q000503:physiopathology*; D011901:Ranvier's Nodes / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D012016:Reference Values; D012684:Sensory Thresholds / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology
D006442:Glycated Hemoglobin; D015222:Sodium Channels