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The Functional Significance of Gap Junction Channels in the Epileptogenicity and Seizure Susceptibility of Juvenile Rats
Author(s) -
Gajda Zita,
Hermesz Edit,
Gyengési Erika,
Szupera Zoltán,
Szente Magdolna
Publication year - 2006
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2006.00573.x
Subject(s) - gap junction , neuroscience , epilepsy , connexin , electrophysiology , biology , messenger rna , medicine , chemistry , endocrinology , microbiology and biotechnology , gene , genetics , intracellular
Summary: Purpose: The functional significance of gap‐junction (GJ) channels in seizure susceptibility and induction and maintenance of seizures in the developing rat brain was investigated on the 4‐aminopyridine (4‐AP) in vivo epilepsy model. Methods: In electrophysiological experiments, GJs were manipulated with a blocker or opener before induction or at the active epileptic foci between postnatal days 9 and 28 (P9–28). Semiquantitative reverse transcriptase–polymerase chain reaction (RT‐PCR) amplification was used to measure the levels of connexin (Cx) 26, 32, 36, and 43 mRNAs at the untreated cortex or epileptic foci. Results: The basic electrocorticogram (ECoG) and Cx messenger RNA (mRNA) expression patterns exhibited characteristic maturation; the 4‐AP–induced epileptiform activity correlated well with these changes. Cx mRNA expressions were significantly upregulated around P16 (except for Cx26). The Cx26, 36, and 43 gene inducibility was highest around P16 and then declined significantly. In the youngest animals, the GJ opener induced rhythmic synchronous cortical activity. On maturation, the seizures became focalized and periodic; the discharges accelerated their amplitude and frequency increase. A transient decrease (P13–14) and then increase (P15–16) in seizure susceptibility were followed by a tendency to periodicity and focalization. Conclusions: The study suggests that GJ communication is involved in rhythm genesis and synchronization of cortical activity and may enhance the epileptogenicity of the developing brain.