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The Journal of Neuroscience, September 17, 2008, 28(38):9349-9362; doi:10.1523/JNEUROSCI.3195-08.2008

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Neurobiology of Disease
Metabolic Environment in Substantia Nigra Reticulata Is Critical for the Expression and Control of Hypoglycemia-Induced Seizures

Libor Velísek,1,2,4 Jana Velísková,1,2,4 Ondrej Chudomel,1 Ka-Lai Poon,1 Kimberly Robeson,1 Barbara Marshall,3 Archana Sharma,1 and Solomon L. Moshé1,2,3,4

1The Saul R. Korey Department of Neurology, 2Dominick P. Purpura Department of Neuroscience, 3Department of Pediatrics, and 4Einstein/Montefiore Comprehensive Epilepsy Management Center, Albert Einstein College of Medicine, Bronx, New York 10461

Correspondence should be addressed to Dr. Libor Velísek, Albert Einstein College of Medicine, 1300 Morris Park Avenue, K 314, Bronx, NY 10461. Email: velisek{at}aecom.yu.edu

Seizures represent a common and serious complication of hypoglycemia. Here we studied mechanisms of control of hypoglycemic seizures induced by insulin injection in fasted and nonfasted rats. We demonstrate that fasting predisposes rats to more rapid and consistent development of hypoglycemic seizures. However, the fasting-induced decrease in baseline blood glucose concentration cannot account for the earlier onset of seizures in fasted versus nonfasted rats. Data obtained with c-Fos immunohistochemistry and [14C]2-deoxyglucose uptake implicate a prominent involvement of the substantia nigra reticulata (SNR) among other structures in the hypoglycemic seizure control. This is supported by data showing that fasting decreases the SNR expression of KATP channels, which link metabolism with activity, and is further confirmed with microinfusions of KATP channel agonist and antagonist. Data obtained with whole-cell and perforated patch recordings from SNR neurons in slices in vitro demonstrate that both presynaptic and postsynaptic KATP channels participate in the failure of the SNR to control hypoglycemic seizures. The results suggest that fasting and insulin-induced hypoglycemia can lead to impairment in the function of the SNR, leading thus to hypoglycemic seizures.

Key words: hypoglycemia; fasting; Kir6.2; substantia nigra; intracellular recordings; 2-deoxyglucose

Received July 9, 2008; accepted July 31, 2008.

Correspondence should be addressed to Dr. Libor Velísek, Albert Einstein College of Medicine, 1300 Morris Park Avenue, K 314, Bronx, NY 10461. Email: velisek{at}aecom.yu.edu


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