title: Interneuronal calcium channel abnormalities in posttraumatic epileptogenic neocortex.
abstract: Decreased release probability (Pr) and increased failure rate for monosynaptic inhibitory postsynaptic currents (IPSCs) indicate abnormalities in presynaptic inhibitory terminals on pyramidal (Pyr) neurons of the undercut (UC) model of posttraumatic epileptogenesis. These indices of inhibition are normalized in high [Ca++] ACSF, suggesting dysfunction of Ca2+ channels in GABAergic terminals. We tested this hypothesis using selective blockers of P/Q and N-type Ca2+ channels whose activation underlies transmitter release in cortical inhibitory terminals. Pharmacologically isolated monosynaptic IPSCs were evoked in layer V Pyr cells by extracellular stimuli in adult rat sensorimotor cortical slices. Local perfusion of 0.2/1 μM ω-agatoxin IVa and/or 1 μM ω-conotoxin GVIA was used to block P/Q and N-type calcium channels, respectively. In control layer V Pyr cells, peak amplitude of eIPSCs was decreased by ~50% after treatment with either 1 μM ω-conotoxin GVIA or 1 μM ω-agatoxin IVa. In contrast, there was a lack of sensitivity to 1 μM ω-conotoxin GVIA in UCs. Immunocytochemical results confirmed decreased perisomatic density of N-channels on Pyr cells in UCs. We suggest that decreased calcium influx via N-type channels in presynaptic GABAergic terminals is a mechanism contributing to decreased inhibitory input onto layer V Pyr cells in this model of cortical posttraumatic epileptogenesis.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Leonardo C
authors.initials: LC
authors.lastname: Faria
authors.forename: Isabel
authors.initials: I
authors.lastname: Parada
authors.forename: David A
authors.initials: DA
authors.lastname: Prince
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D004827:Epilepsy / Q000209:etiology / Q000378:metabolism*; D007150:Immunohistochemistry; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008297:Male; D019579:Neocortex / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015220:Calcium Channels