Quinine suppresses extracellular potassium transients and ictal epileptiform activity without decreasing neuronal excitability in vitro.
The effect of quinine on pyramidal cell intrinsic properties, extracellular potassium transients, and epileptiform activity was studied in vitro using the rat hippocampal slice preparation. Quinine enhanced excitatory post-synaptic potentials and decreased fast- and slow-inhibitory post-synaptic potentials. Quinine reduced the peak potassium rise following tetanic stimulation but did not affect the potassium clearance rate. Epileptiform activity induced by either low-Ca(2+) or high-K(+) artificial cerebrospinal fluid (ACSF) was suppressed by quinine. The frequency of spontaneous inter-ictal bursting induced by picrotoxin, high-K(+), or 4-aminopyridine was significantly increased. In normal ACSF, quinine did not affect CA1 pyramidal cell resting membrane potential, input resistance, threshold for action potentials triggered by intracellular or extracellular stimulation, or the orthodromic and antidromic evoked population spike amplitude. The main effects of quinine on intrinsic cell properties were to increase action potential duration and to reduce firing frequency during sustained membrane depolarizations, but not at normal resting membrane potentials. This attenuation was enhanced at increasingly depolarized membrane potentials. These results suggest that quinine suppresses extracellular potassium transients and ictal activity and modulates inter-ictal activity by limiting the firing rate of cells in a voltage-dependent manner. Because quinine does not affect 'normal' neuronal function, it may merit consideration as an anticonvulsant.
Bikson
M
M
Division of Neuroscience (Neurophysiology), University of Birmingham School of Medicine, Egbaston, Birmingham B15 2TT, UK. j.g.r.jefferys@bham.ac.uk
Id Bihi
R
R
Vreugdenhil
M
M
Köhling
R
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Fox
J E
JE
Jefferys
J G R
JG
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D005110:Extracellular Space / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D011803:Quinine / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; D015221:Potassium Channels; D011803:Quinine