Cyclothiazide prolongs low [Mg2+]-induced seizure-like events.

Abstract

Here we address the effects of cyclothiazide (CTZ), an allosteric inhibitor of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor desensitization, on low [Mg(2+)]-induced seizure-like events (SLEs) recorded from the CA3 pyramidal layer of juvenile rat hippocampal slices. CTZ (100 microM) made the period of tonic-like discharges (161 +/- 18% of control) and the whole SLE (151 +/- 15% of control) longer (in 7 of 9 slices) or induced endless SLE by stabilizing clonic-like bursting (in 2 of 9 slices). CTZ (30 microM) had no significant effects on SLE dynamics (n = 4), whereas 300 microM CTZ induced endless SLEs in four of eight slices. Co-application of CTZ (100 microM) with 100 microM GYKI-52466, the allosteric inhibitor of AMPA receptor function, restrained the effects of CTZ and shortened SLEs and their tonic phases to 37 +/- 4.2 and 47 +/- 4.2% of the control, respectively. Effects of GYKI-52466 and GYKI-52466 with CTZ on SLE dynamics were indistinguishable. 4-aminopyridine (4-AP; 50 microM) alone (n = 5) or in combination with CTZ (n = 6) transformed recurrent SLE pattern into incessant epileptiform activity with patterns distinguishable from those under 100 microM CTZ application. The effect of 4-AP may suggest a role for facilitated presynaptic glutamate release in disrupting recurrent dynamics. In contrast, the self-similar slow-down of low [Mg(2+)]-induced SLE dynamics by CTZ indicate AMPA receptor desensitization as a parameter shaping SLEs.

• Authors: Bálint Lasztóczi, Julianna Kardos
• Journal: Journal of neurophysiology (J Neurophysiol) Vol. 96 Issue 6 Pg. 3538-44 (Dec 2006) ISSN: 0022-3077 [Print] United States
• PMID: 16914619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzothiadiazines
• Diuretics
• Excitatory Amino Acid Antagonists
• Potassium Channel Blockers
• Receptors, AMPA
• Receptors, Presynaptic
• GYKI 52466
• Benzodiazepines
• Glutamic Acid
• 4-Aminopyridine
• cyclothiazide

Topics

• 4-Aminopyridine (pharmacology)
• Animals
• Benzodiazepines (pharmacology)
• Benzothiadiazines (pharmacology)
• Diuretics (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Glutamic Acid (metabolism)
• Hippocampus (cytology, drug effects, physiology)
• Magnesium Deficiency (physiopathology)
• Male
• Potassium Channel Blockers (pharmacology)
• Pyramidal Cells (drug effects)
• Rats
• Rats, Wistar
• Receptors, AMPA (antagonists & inhibitors)
• Receptors, Presynaptic (drug effects, metabolism)
• Seizures (chemically induced, physiopathology)