ETHANOL INHIBITION OF REDUCED FREQUENCY-DEPENDENT RUNDOWN OF CALCIUM CURRENTS IN ACUTELY DISSOCIATED MS NDB NEURONS FROM CHRONIC IN-VIVO LEAD-EXPOSED ADULT-RATS/

Although it is well known that lead (Pb2+) acutely blocks voltage-gate d calcium currents (VGCCs) in mammalian neurons,little is known about the long-term effects of continuous exposure to this metal on VGCCs. I n the present study, the effects of chronic lead exposure on VGCCs (wi th barium ions as the charge carrier) were studied using whole-cell pa tch-clamp electrophysiological techniques in acutely dissociated media l septum (MS)/nucleus diagonal band (nDB) neurons. Neither peak, end c urrent amplitudes, nor the current-voltage relationship were affected by chronic lead exposure. However, VGCCs repetitively evoked at freque nt 6 s intervals displayed diminished whole-cell current rundown after 2 min of stimulation in cells from chronic Pb-exposed rats compared t o cells from control Na-exposed rats. Because rundown after repetitive stimulation at a slower rate (20 s intervals) was not different betwe en Pb-exposed and Na-exposed, reduced rundown at 6 s intervals was pro bably due to decreased slow inactivation of voltage-gated calcium chan nels. Interestingly, acute application of 60 mM ethanol reversed the r educed rundown in cells from Pb-exposed rats while having no effect on cells from Na-exposed rats. Clearly, acute ethanol treatment antagoni zed the effect of chronic lead exposure, unlike the additive interacti on we observed previously with synaptic plasticity (Grover and Frye, 1 996). Acute application of 1 mu M Pb2+ completely blocked VGCCs simila rly in neurons from Na-exposed and Pb-exposed rats. These findings do not suggest that major adaptive changes in VGCCs have occurred during chronic in vivo exposure to lead. But, subtle changes in channel effic iency only revealed under conditions of repetitive stimulation may exi st, and are reversed by ethanol. These subtle changes may be sufficien t to influence neuroplasticity such as LTP. (C) 1997 Intox Press, Inc.