Sensitivity of cerebellar Purkinje neurons to neurotransmitters in genetically epileptic rats.
Epilepsy is a state of neuronal hyperactivity which may be caused by an altered relationship between inhibitory and excitatory influences on neurons. We have conducted experiments using microiontophoresis with in situ extracellular recording of anesthetized rat cerebellar Purkinje neuron activity to determine the sensitivity of these neurons to neurotransmitters in a genetic model of epilepsy. Quantitative evaluations of agonist-induced changes in activity were carried out by using poststimulus time histograms. Current-response curves were generated and linear regression analysis was performed to evaluate changes in responsiveness and sensitivity between control and genetically epilepsy-prone-9 rats. The current required to produce 50% inhibition of activity by GABA was 2.6-fold higher in the genetically epilepsy-prone-9 rats compared to control. In contrast, the amount of current required to produce 50% inhibition by norepinephrine was not significantly different between groups. There also was no significant change in cerebellar neuron sensitivity to the excitatory transmitter, glutamate. The lack of an alteration in sensitivity and responsiveness to norepinephrine or glutamate suggests that the hyperexcitability of neurons may be associated with a specific subsensitivity of the GABAergic system. Such a specific subsensitivity to gamma-aminobutyric acid would, therefore, yield a more excitable state of the neuron and may contribute to the development of the hyperactivity observed in epilepsy.
Department of Pharmacology and Toxicology, West Virginia University, Morgantown.
E M
EM
Gould
C R
CR
Craig
W W
WW
Fleming
D A
DA
Taylor
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D004594:Electrophysiology; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007478:Iontophoresis; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D005971:Glutamates; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid