PURPOSE: γ-Aminobutyric acid (GABA)ergic transmission plays an important role in the initiation of epileptic activity and the generation of ictal discharges. The functional alterations in the epileptiform hippocampus critically depend on GABAergic mechanisms and cation-chloride cotransporters. METHODS: To understand the cellular basis of specific functional alterations in the epileptic hippocampus, we studied physiologic characteristics and pharmacologically isolated evoked GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) recorded from principal neurons in hippocampal slices from status epilepticus (SE) and control rats using whole-cell and gramicidin perforated patch-clamp recordings. KEY FINDINGS: Whereas the resting membrane potential and input resistance were not significantly different between control and epileptic tissue, the reversal potential (E(GABA) ) of IPSCs was significantly shifted to more positive values in SE rats with regard to the resting membrane potential. Pharmacologic experiments and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) showed that the observed changes in the epileptic tissue were due to a decreased ratio of the main Cl(-) extrusion transporter (K(+) -Cl(-) cotransporter, KCC2) to the main Cl(-) uptake transporter (Na(+) -K(+) -2Cl(-) cotransporter, NKCC1). SIGNIFICANCE: Our results suggest that alterations of cation-chloride cotransporter functions, comprising a higher NKCC1 action, contribute to hyperexcitability within the hippocampus following SE. Wiley Periodicals, Inc.
PURPOSE: γ-Aminobutyric acid (GABA)ergic transmission plays an important role in the initiation of epileptic activity and the generation of ictal discharges. The functional alterations in the epileptiform hippocampus critically depend on GABAergic mechanisms and cation-chloride cotransporters. METHODS: To understand the cellular basis of specific functional alterations in the epileptic hippocampus, we studied physiologic characteristics and pharmacologically isolated evoked GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) recorded from principal neurons in hippocampal slices from status epilepticus (SE) and control rats using whole-cell and gramicidin perforated patch-clamp recordings. KEY FINDINGS: Whereas the resting membrane potential and input resistance were not significantly different between control and epileptic tissue, the reversal potential (E(GABA) ) of IPSCs was significantly shifted to more positive values in SE rats with regard to the resting membrane potential. Pharmacologic experiments and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) showed that the observed changes in the epileptic tissue were due to a decreased ratio of the main Cl(-) extrusion transporter (K(+) -Cl(-) cotransporter, KCC2) to the main Cl(-) uptake transporter (Na(+) -K(+) -2Cl(-) cotransporter, NKCC1). SIGNIFICANCE: Our results suggest that alterations of cation-chloride cotransporter functions, comprising a higher NKCC1 action, contribute to hyperexcitability within the hippocampus following SE. Wiley Periodicals, Inc.
Authors: Susan L Campbell; Stefanie Robel; Vishnu A Cuddapah; Stephanie Robert; Susan C Buckingham; Kristopher T Kahle; Harald Sontheimer Journal: Glia Date: 2014-07-26 Impact factor: 7.452
Authors: Matthew R Kelley; Tarek Z Deeb; Nicholas J Brandon; John Dunlop; Paul A Davies; Stephen J Moss Journal: Neuropharmacology Date: 2016-04-21 Impact factor: 5.250
Authors: Liliya Silayeva; Tarek Z Deeb; Rochelle M Hines; Matt R Kelley; Michaelanne B Munoz; Henry H C Lee; Nicholas J Brandon; John Dunlop; Jaime Maguire; Paul A Davies; Stephen J Moss Journal: Proc Natl Acad Sci U S A Date: 2015-03-02 Impact factor: 11.205
Authors: Jyun-You Liou; Hongtao Ma; Michael Wenzel; Mingrui Zhao; Eliza Baird-Daniel; Elliot H Smith; Andy Daniel; Ronald Emerson; Rafael Yuste; Theodore H Schwartz; Catherine A Schevon Journal: Brain Date: 2018-07-01 Impact factor: 13.501
Authors: Yogendra H Raol; Srdjan M Joksimovic; Dayalan Sampath; Brock A Matter; Philip M Lam; Uday B Kompella; Slobodan M Todorovic; Marco I González Journal: Neurosci Lett Date: 2020-08-26 Impact factor: 3.046