| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1986: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1985: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
The giant axon of the crayfish, Cambarus clarkii, was used in Van Harreveld's solution, and the maximum rate of rise of the action potential was taken as a measure of the sodium current. The viscosity effect and the osmotic effect inevitably caused from a high concentration of glucose were estimated using an inert substance of sucrose as their controls, and were subtracted for its pharmacological effect. Effect of glucose on the sodium current was examined in its concentrations lower than 278 mM to avoid some deleterious effect. The n and Kd values were 1.17 <-!+> 0.106 and 1318 <-!+> 213 mM (mean <-!+> SE, 10 axons) at a temperature of 10 <-!+> 0.3 ゜C. The experiments were repeated at different temperatures in a range of 5 to 23 ゜C. The heat of the binding reaction as calculated by the van't Hoff equation averages 19.7 kcal/mole (n=14), suggesting the involvement of multiple hydrogen bonds between the hydroxyl groups of the glucose molecule and the Na channel receptor. The potency of the glucose effect suppressing the sodium current was significantly higher than those of the stereoisomers such as mannose, galactose and alpha-D-glucose, indicating a high stereospecificity of the glucose molecule in its action. The glucose effect had a nearly constant potency over pH 5 to 7. Glucose did not affect significantly the dissociation constant of <Na^+> - <Na^+> binding complex in its permeation processes which was determined based on a steady-state kinetic model developed for this special analysis. It is concluded that glucose blocks the sodium chennel not by altering the conformation of the channel proteins but by simply plugging its mouth.
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