|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1996 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1995 : ¥1,400,000 (Direct Cost : ¥1,400,000)
We studied the pathophysiology of suppression of voltage-dependent potassium channel (VDKC) using patch clamp method in Isaacs'syndrome. We also studied the existence of anti-VDKC autoantibody using molecular biologgical mehods in patients with Isaacs'syndrome and related disordes.
In additon to PC12, VDCK of NB1 cell co-cultured with patients immunoglobulin and standard medium for 3 days was also suppressed using pathch clamp method. In outward potassium currents, peak current, corresponded to fast K+ channel which is generated immediatery after stimulation, was more suppressed than steady state current, mainly corresponded to slow K+ channel. These findings suggest that antiboy in patients with Isaacs'syndrome seems to mainly block fatst K+ channel. This speculation is concistent with the findins that antigen protein, reacted withpatients'sera, cross-linked with dendrotoxin, which is one of the blocker of fast K+ channel. Furthermore, we investigated the effects of patients'sera on voltage-dependent sodium channel (VDNC) in NB1 cells, however, suppression or activation of VDNC were not seen. Therefore, hyperexcitability of peripheral nerve in Isaacs'syndrome is not due to activation of VDNC but suppresion of VDKC by autoantibody. On the other hand, in some patients with idiopathic generalized myokymia, who shows only myokymia and mild muscle cramp without typical symptome seen in Isaacs'syndrome, antibody which suppressed VDKC of NB1 cell was existed. Furthermore, in early course of Guillain-Barre syndrome, autoantibody to VDKC was also exicted and may correlate to myokymia and dysesthesia seen in early stage of this syndrome.