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Biophysics Sector, International School for Advanced Studies (SISSA), Trieste, Italy.

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 micrograms 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 microM), 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.

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