Abnormal electric membrane properties of Down's syndrome DRG neurons in cell culture

Cell cultures were prepared from normal and Down's syndrome dorsal root ganglia (DRG). Both pre- and postnatal specimens were utilized; 8 normal and 4 Down's. Cultures were maintained in medium with normal (4 mM) and elevated (20 mM) potassium (K) since the latter was found to enhance neuron survival. After various period of incubation, cultures were transferred to normal K medium and their electrical membrane properties (EMP) determined using intracellular recording techniques. An analysis of variance was performed with 5 covariates: developmental stage, culture duration, K concentration, type of action potential, and neuronal surface area. This analysis indicated that the Down's neurons had abnormal EMP, the most affected being the after hyperpolarization (-41%), membrane time constant (+30%), threshold rheobasic depolarization (-22%), rate of falling phase of action potential (-20%), specific membrane resistance (+18%) and absolute refractory period (+12%). All differences were also observed when samples of normal and Down's neurons were matched for the 5 covariates mentioned above, take separately. If the abnormal EMP observed in the present study for Down's DRG neurons in culture occurred for CNS neurons in situ they would disrupt the normal function of the nervous system and could therefore constitute the neurobiological basis of the mental retardation observed in Down's syndrome.