IMMUNOGLOBULINS FROM MOTONEURON DISEASE PATIENTS ENHANCE GLUTAMATE RELEASE FROM RAT HIPPOCAMPAL-NEURONS IN CULTURE

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 cu rrents in rat hippocampal cells in culture. 2. Focal application of AL S IgGs (100 mu g ml(-1)) to hippocampal cells induced a rise in freque ncy but not in amplitude of spontaneous excitatory postsynaptic curren ts (SEPSC) which outlasted the period of IgG application. The mean fre quency ratio (ALS over control) was 3.2 +/- 0.6 (n = 19). No changes i n frequency or amplitude of SEPSCs were observed after treatment with IgGs obtained from healthy donors (n = 5) or from patients with Alzhei mer'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 p ostsynaptic 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 di d not modify the amplitude or the shape of currents evoked by AMPA (10 0 mu M), recorded at a holding potential of -50 mV. 5. It is concluded that ALS IgGs enhance both SEPSCs and mEPSCs through a presynaptic ty pe of action. The excessive release of glutamate from nerve endings ma y be the cause of motoneurone death in ALS patients.