Immunoglobulins from motoneurone disease patients enhance glutamate release from rat hippocampal neurones in culture

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Abstract
1 The whole-cell configuration of the patch-clamp technique was used to study the effects of immunoglobulins (IgGs) from patients affected by amyotrophic lateral sclerosis (ALS) on spontaneous glutamatergic currents in rat hippocampal cells in culture. 2 Focal application of ALS IgGs (100 μg ml−1) to hippocampal cells induced a rise in frequency but not in amplitude of spontaneous excitatory postsynaptic currents (SEPSC) which outlasted the period of IgG application. The mean frequency ratio (ALS over control) was 3.2 ± 0.6 (n. 19). No changes in frequency or amplitude of SEPSCs were observed after treatment with IgGs obtained from healthy donors (n=5) or from patients with Alzheimer's disease (n=4). 3 ALS IgGs also increased the frequency (by a factor of 2.0 ± 0.3) but not the amplitude of miniature excitatory postsynaptic currents (mEPSC) recorded in the presence of TTX (n=19). A rise in frequency of mEPSC was also seen in cells superfused with a calcium-free solution (n=4). 4 In the presence of TTX, ALS IgGs did not modify the amplitude or the shape of currents evoked by AMPA (100 μm), recorded at a holding potential of −50 mV. 5 It is concluded that ALS IgGs enhance both SEPSCs and mEPSCs through a presynaptic type of action. The excessive release of glutamate from nerve endings may be the cause of motoneurone death in ALS patients.