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+0 acutely blocks voltage-gated calcium currents (VGCCs) in mammalian neurons, little is known about the long-term effects of continuous exposure to this metal on VGCCs. In the present study, the effects of chronic lead exposure on VGCCs (with barium ions as the charge carrier) were studied using whole-cell patch-clamp electrophysiological techniques in acutely dissociated medial septum (MS)/nucleus diagonal band (nDB) neurons. Neither peak, end current amplitudes, nor the current-voltage relationship were affected by chronic lead exposure. However, VGCCs repetitively evoked at frequent 6 s intervals displayed diminished whole-cell current rundown after 2 min of stimulation in cells from chronic Pb-exposed rats compared to cells from control Na-exposed rats. Because rundown after repetitive stimulation at a slower rate (20 s intervals) was not different between Pb-exposed and Na-exposed, reduced rundown at 6 s intervals was probably due to decreased slow inactivation of voltage-gated calcium channels. Interestingly, acute application of 60 mM ethanol reversed the reduced rundown in cells from Pb-exposed rats while having no effect on cells from Na-exposed rats. Clearly, acute ethanol treatment antagonized the effect of chronic lead exposure, unlike the additive interaction we observed previously with synaptic plasticity (Grover and Frye, 1996). Acute application of 1 microM Pb2+ completely blocked VGCCs similarly 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 efficiency only revealed under conditions of repetitive stimulation may exist, and are reversed by ethanol. These subtle changes may be sufficient to influence neuroplasticity such as LTP.
Grover
C A
CA
Department of Medical Pharmacology, Texas A&M University HSC College Station 77843-1114, USA.
Jasek
M C
MC
Frye
G D
GD
Griffith
W H
WH
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000633:toxicity*; D000431:Ethanol / Q000494:pharmacology*; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects*; D015640:Ion Channel Gating / Q000187:drug effects; D007854:Lead / Q000097:blood; D007855:Lead Poisoning / Q000097:blood*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012688:Septum Pellucidum / Q000166:cytology / Q000187:drug effects*
D002121:Calcium Channel Blockers; D007854:Lead; D000431:Ethanol