PILOCARPINE AND KAINATE CHANGE SUBSTANTIA NIGRA PARS RETICULATA GABAergic NEURONS ACTIVITY
Abstract number :
1.073
Submission category :
Year :
2002
Submission ID :
1568
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Olga I. Claudio, Solomon L. Moshe. Neurology, Albert Einstein College of Medicine, Bronx, NY; Neurosciences, Albert Einstein College of Medicine, Bronx, NY; Pediatrics, Albert Einstein College of Medicine, Bronx, NY
RATIONALE: The substantia nigra pars reticulata (SNR) mediates seizure control. The study of the cellular substrates involved in the SNR mediated seizure control would provide the knowledge to obtain new therapies that will allow for the better management and control of seizures. However, in vitro models of SNR epileptiform activity that would help in the identification of these substrates have not been developed. In this study we bath applied two known convulsants with the purpose obtaining a workable in vitro model of SNR epileptiform activity to aid in the identification of these cellular substrates.
METHODS: Sagittal slices from PN 14-17 male Sprague Dawley rats were obtained using a sucrose-based buffer and a vibratome and perfused in oxygenated (95% O2 / 5% CO2) artificial cerebrospinal fluid at room temperature. Visually -guided recordings from SNR neurons were performed using the technique of whole cell perforated patch clamp recording with the cation - permeable ionophore gramicidin to avoid perturbations of intracellular chloride by the electrode. Pilocarpine (5 mM) and kainic acid (5[mu]M) were dissolved in ACSF and bath - applied.
RESULTS: Bath application of both agents induced depolarization and increased firing rate of SNR GABAergic neurons within 2 minutes of application. The effect of pilocarpine was still present 1 hour after washout of the drug. Washout of kainic acid led to restoration of normal firing rate after 30 minutes. However, membrane potential remained depolarized.
CONCLUSIONS: Pilocarpine and kainic acid depolarize and increase the firing rate of SNR GABAergic neurons. With the concentrations used, the effect of pilocarpine was more persistent than the effect of kainic acid. Membrane potential remains depolarized after washout of pilocarpine or kainate, suggesting that neurons could be more susceptible to a subsequent excitatory stimulus.
[Supported by: NINDS NS 20253 and NS 36238. Dr. Olga I. Claudio is the recipient of the E. W. Lothman Award 2002 from the Epilepsy Foundation of America.]