Korean J Physiol Pharmacol.
1999 Feb;3(1):101-117.
The effects of sera from amyotrophic lateral sclerosis patients on neuromuscular transmission and calcium channels in mice
- Affiliations
-
- 1Department of Physiology and Biophysics, Seoul National University College of Medicine, 28 Yongo South Korea.
Abstract
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Amyotrophic lateral sclerosis (ALS) is a degenerative neuromuscular
disease of unknown etiology in which the upper and lower motor neurons
are progressively destroyed. Recent evidences support the role of
autoimmune mechanisms in the pathogenesis of ALS. This study
investigated the effects of sera from ALS patients on neuromuscular
transmission in phrenic nerve-hemidiaphragm preparations and on calcium
currents of single isolated dorsal root ganglion (DRG) cells in mice.
Mice were injected with either control sera from healthy adults or ALS
sera from 18 patients with ALS of sporadic form, for three days.
Miniature end plate potential (MEPP) and nerve-evoked end plate
potential (EPP) were measured using intracellular recording technique
and the quantal content was determined. Single isolated DRG cells were
voltage-clamped with the whole-cell configuration and membrane currents
were recorded. Sera from 14 of 18 ALS patients caused a significant
increase in MEPP frequency in normal Ringer's solution (4.62+/-0.14 Hz)
compared with the control (2.18+/-0.15 Hz). In a high Mg2+/low Ca2+
solution, sera from 13 of 18 ALS patients caused a significant increase
in MEPP frequency, from 2.18+/-0.31 Hz to 6.09+/-0.38 Hz. Sera from 11 of
18 patients produced a significant increase of nerve-evoked EPP
amplitude, from 0.92+/-0.05 mV to 1.30+/-0.04 mV, while the other seven
ALS sera did not alter EPP amplitude. In the ALS group, EPP quantal
content was also elevated by the sera of 14 patients (from 1.49+/-0.07
to 2.35+/-0.07). MEPP frequency and amplitude in wobbler mouse were
4.03+/-0.53 Hz and 1.37+/-0.18 mV, respectively, which were significantly
higher than those of wobbler controls (wobblers without the symptoms of
wobbler). Sera from ALS patients significantly reduced HVA calcium
currents of DRG cells to 42.7% at -10 mV. Furthermore, the inactivation
curve shifted to more negative potentials with its half-inactivation
potential changed by 6.98 mV. There were, however, significant changes
neither in the reversal potential of ICa nor in the I-V curve. From
these results it was concluded that: 1) The serum factors of sporadic
ALS patients increase neuromuscular transmission and can alter motor
nerve terminal presynaptic function. This suggests that ALS serum
factors may play an important role in the early stage of ALS, and 2)
Calcium currents in DRG cells were reduced and rapidly inactivated by
ALS sera, suggesting that in these cells, ALS serum factors may exert
interaction with the calcium channel.