Function of Inhibitory Micronetworks Is Spared by Na(+) Channel-Acting Anticonvulsant Drugs

Autor: Carolin Miklitz, Liset Menendez de la Prida, Robert G. Averkin, Heinz Beck, Christina Müller, Stefan Remy, Mischa Uebachs, Elisa Bellistri, Leonie Pothmann
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Patch-Clamp Techniques
medicine.medical_treatment
Hippocampus
Convulsants
Pharmacology
pharmacology [Carbamazepine]
pathology [Epilepsy]
toxicity [Pilocarpine]
Sodium Channels
Membrane Potentials
Neurons
Kainic Acid
Chemistry
General Neuroscience
Pilocarpine
Articles
physiology [Membrane Potentials]
chemically induced [Epilepsy]
Carbamazepine
Excitatory postsynaptic potential
GABAergic
Anticonvulsants
drug effects [Inhibitory Postsynaptic Potentials]
Biophysics
In Vitro Techniques
Inhibitory postsynaptic potential
therapeutic use [Anticonvulsants]
In vivo
drug effects [Nerve Net]
medicine
drug effects [Neurons]
Animals
Channel blocker
ddc:610
Rats
Wistar
toxicity [Convulsants]
Epilepsy
drug effects [Membrane Potentials]
Neural Inhibition
Electric Stimulation
Rats
Electrophysiology
Disease Models
Animal
Anticonvulsant
drug effects [Neural Inhibition]
Inhibitory Postsynaptic Potentials
pharmacology [Anticonvulsants]
cytology [Hippocampus]
Nerve Net
toxicity [Kainic Acid]
metabolism [Sodium Channels]
Neuroscience
Zdroj: The journal of neuroscience 34(29), 9720-9735 (2014). doi:10.1523/JNEUROSCI.2395-13.2014
DOI: 10.1523/JNEUROSCI.2395-13.2014
Popis: The mechanisms of action of many CNS drugs have been studied extensively on the level of their target proteins, but the effects of these compounds on the level of complex CNS networks that are composed of different types of excitatory and inhibitory neurons are not well understood. Many currently used anticonvulsant drugs are known to exert potent use-dependent blocking effects on voltage-gated Na(+) channels, which are thought to underlie the inhibition of pathological high-frequency firing. However, some GABAergic inhibitory neurons are capable of firing at very high rates, suggesting that these anticonvulsants should cause impaired GABAergic inhibition. We have, therefore, studied the effects of anticonvulsant drugs acting via use-dependent block of voltage-gated Na(+) channels on GABAergic inhibitory micronetworks in the rodent hippocampus. We find that firing of pyramidal neurons is reliably inhibited in a use-dependent manner by the prototypical Na(+) channel blocker carbamazepine. In contrast, a combination of intrinsic and synaptic properties renders synaptically driven firing of interneurons essentially insensitive to this anticonvulsant. In addition, a combination of voltage imaging and electrophysiological experiments reveal that GABAergic feedforward and feedback inhibition is unaffected by carbamazepine and additional commonly used Na(+) channel-acting anticonvulsants, both in control and epileptic animals. Moreover, inhibition in control and epileptic rats recruited by in vivo activity patterns was similarly unaffected. These results suggest that sparing of inhibition is an important principle underlying the powerful reduction of CNS excitability exerted by anticonvulsant drugs.
Databáze: OpenAIRE
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