| Project/Area Number |
05670555
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Shiga University of Medical Science |
|---|
Principal Investigator |
YASUDA Hitoshi Shiga University of Medical Science Third Department of Medicine, Assistant Professor, 医学部, 講師 (80135467)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TERADA Masahiko Shiga University of Medical Science, Third Department of Medicine, Instructor, 医学部, 助手 (00227521)
KITASATO Hiroshi Shiga University of Medical Science, Second Department of Physiology, Professor, 医学部, 教授 (20079700)
|
|---|
| Project Period (FY) |
1993 – 1994
|
| Project Status |
Completed (Fiscal Year 1994)
|
| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | Motor neuron disease / Diabetic neuropathy / Single myelinated nerve fiber / Voltage clamp / Ion channel / Anti-GM1 antibody / Glucose / Ketone bodies / ギラン・バレー症候群 / 抗GM1抗体 / ランヴィエ絞輪 / Na^+電流低下 / K^+電流増加 / ラット / ワセリンギャップ法 / 膜電位固定法 |
|---|
| Research Abstract |
(1) The pathogenic role of anti-GM1 antibody was examined using the vaseline-gap voltage clamp technique on isolated single myelinated rat nerve fibers. Anti-GM1 antisera were obtained from rabbits immunized with GM1 ganglioside. Extracellularly applied anti-GM1 antisera without complement activity increased both the rate of rise and the amplitude of the K+ current elicited with little affect on Na current. In the presence of active complement, anti-GM1 antibodies decreased the Na current, and caused a progressive increase of non-specific leakage current. The results indicate that anti-GM1 antibodies can uncover K^+ channels in the paranodal region and antibody-complement complexes may block Na^+ channels and disrupts the membrane at the Ranvier.
(2) The effect of high glucose, fatty acids and ketone bodies on nerve fibers was examined. After external application of D-glucose, action potential and Na^+ current reduced in amplitude at the concentration of glucose higher than 30 mM.The effect of L-glucose was greater than that of D-glucose. After application of 20mM acetoacetic acid, inward Na^+ current decreased and undershoot markedly increased. The application of 20mM 3-hydroxybutyric acid induced a decrease of Na+ current and an increase of K^+ current. These results suggest that high glucose and ketone bodies play important roles in the development of nerve dysfunction by affecting electrophysiological activity of myelinated nerve fibers.
|
