The effect of paxilline on early alterations of electrophysiological properties of dentate gyrus granule cells in pilocarpine-treated rats.
The dentate gyrus of hippocampus has long been considered as a focal point for studies on mechanisms responsible for the development of temporal lobe epilepsy (TLE). Change in intrinsic properties of dentate gyrus granule cells (GCs) has been considered as an important factor responsible in temporal lobe seizures. In this study, we evaluated the intrinsic properties of GCs, during acute phase of seizure (24 h after i.p. injection of pilocarpine) compared to sham group using whole cell patch-clamp recordings. Our results showed a significant increase in the number of action potentials (APs) after applying depolarizing currents of 200 pA (p < 0.01) and 250pA (p < 0.05) compared to sham group. The evaluation of AP properties revealed a decrease in half-width of AP in GCs of seizure group (1.27 ± 0.03 ms) compared to sham group (1.60 ± 0.11). Moreover, addition of BAPTA to pipette solution prevented changes in AP half-width in seizure group (1.71 ± 0.11 ms) compared to sham group (1.91 ± 0.08 ms). In contrast, an increase in the amplitude of fast afterhyperpolarization was observed in GCs of seizure group (-11.68 ± 0.72 mV) compared to sham group (-8.28 ± 0.59 mV). Also, GCs of seizure group showed a significant increase in both firing rate and instantaneous firing frequency at depolarizing currents of 200 pA (P < 0.01) and 250 pA (P < 0.05) compared to sham group. The changes in electrophysiological properties of GCs were attenuated after bath application of paxilline suggesting possible involvement of large conductance Ca(2+)- activated K(+) channel (BK channel). Our results suggested the possible involvement of certain potassium channels in early changes of intrinsic properties of GCs which eventually facilitate TLE development.
Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Nasrin
N
Mehranfard
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hamid
H
Gholamipour-Badie
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Fereshteh
F
Motamedi
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mahyar
M
Janahmadi
Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Nima
N
Naderi
Dentate gyrus; Epilepsy; Granule cells; Paxilline