The action of valproate on spontaneous epileptiform activity in the absence of synaptic transmission and on evoked changes in [Ca2+]o and [K+]o in the hippocampal slice |
| |
Authors: | S Franceschetti B Hamon and U Heinemann |
| |
Institution: | aInstituto Neurologico C. Besta, Milan ,Italy bAbteilung Neurophysiologie, Max Planck Institut fu¨r Psychiatrie, Planegg-Martinsried ,F.R.G. |
| |
Abstract: | The effects of valproate (VPA) on neuronal excitability and on changes in extracellular potassium (K+]0) and calcium (Ca2+]0) were investigated with ion selective-reference electrode pairs in area CA1 of rat hippocampal slices. Field potential responses to single ortho- and antidromic stimuli were unaltered by VPA (1–5 mM). The afferent volley evoked in the Schaffer-commissural fibers was also unaffected. In contrast, VPA (1 mM) depressed frequency potentiation and paired pulse facilitation markedly. Decreases in Ca2+]0 induced either by repetitive stimulation or by application of the excitatory amino acids N-methyl-d-aspartate and quisqualate were reduced, and the latter results suggest that VPA interferes with postsynaptic Ca2+ entry. When synaptic transmission was blocked by lowering Ca2+]0 (0.2 mM) and elevating Mg2+]0 (7 mM), prolonged afterdischarges elicited by antidromic stimulation were blocked by VPA. VPA also suppressed the spontaneous epileptiform activity seen when Ca2+]0 was lowered to 0.2 mM, without elevating Mg2+]0. The amplitudes of the rises in K+]0 induced by repetitive orthodromic stimulation were only slightly depressed and those elicited by antidromic stimulation were generally unaltered by VPA, as were laminar profiles of stimulus-evoked K+]0 signals. These results indicate that VPA has membrane actions in addition to known effects on excitatory and inhibitory transmitter pools. |
| |
Keywords: | Valproate Hippocampus Rat Neuronal excitability [K+]0 [Ca+]0 Spontaneous epileptiform activity |
本文献已被 ScienceDirect 等数据库收录! |
|