Recent evidence indicates that long-chain polyunsaturated fatty acids (PUFAs) can prevent cardiac arrhythmias by a reduction of cardiomyocyte excitability. This was shown to be due to a modulation of the voltage-dependent inactivation of both sodium (INa) and calcium (ICa) currents. To establish whether PUFAs also regulate neuronal excitability, the effects of PUFAs on INa and ICa were assessed in CAl neurons freshly isolated from the rat hippocampus. Extracellular application of PUFAs produced a concentrationdependent shift of the voltage dependence of inactivation of both INa and ICa to more hyperpolarized potentials. Consequently, they accelerated the inactivation and retarded the recovery from inactivation. The EC50 for the shift of the INa steady-state inactivation curve was 2.1 + 0.4 ,uM for docosahexaenoic acid (DHA) and 4 + 0.4 ,uM for eicosapentaenoic acid (EPA). The EC50 for the shift on the ICa inactivation curve was 2.1 + 0.4 for DHA and >15 ,uM for EPA. Additionally, DHA
To explore non-synaptic mechanisms in paroxysmal discharges, we used a computer model of a simplified hippocampal pyramidal cell, surrounded by interstitial space and a "glial-endothelial" buffer system. Ion channels for Na+, K+, Ca2+ and Cl- ion antiport 3Na/Ca, and "active" ion pumps were represented in the neuron membrane. The glia had "leak" conductances and an ion pump. Fluxes, concentration changes and cell swelling were computed. The neuron was stimulated by injecting current. Afterdischarge (AD) followed stimulation if depolarization due to rising interstitial K+ concentration ([K+]o) activated persistent Na+ current (INa.P). AD was either simple or self-regenerating; either regular (tonic) or burst-type (clonic); and always self-limiting. Self-regenerating AD required sufficient INa.P to ensure re-excitation. Burst firing depended on activation of dendritic Ca2+ currents and Ca-dependent K+ current. Varying glial buffer function influenced [K+]o accumulation and afterdischarge duration. Variations in Na+ and K+ currents influenced the threshold and the duration of AD. The data show that high [K+]o and intrinsic membrane currents can produce the feedback of self-regenerating afterdischarges without synaptic input. The simulated discharge resembles neuron behavior during paroxysmal firing in living brain tissue.
Calcium currents in pyramidal CA1 neurons in vitro after kindling epileptogenesis in the hippocampus of the rat Faas, G.C.; Vreugdenhil, M.; Wadman, W.J.
Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract--Calcium is an important second messenger which plays a role in the regulation of neuronal excitability and in many forms of synaptic plasticity. In kindling epileptogenesis, a model of focal epilepsy, calcium plays an important role. The in situ patch-clamp technique was used to record calcium currents in slices obtained from kindled rats and controls. We found that low-voltage-activated calcium currents, probably of dendritic origin, were larger after kindling (80%). The transient high-voltage-activated calcium currents were also enhanced after kindling (50% higher). The increase of the current is accompanied by a decrease in the time constant of inactivation. The change was still present six weeks after the kindling stimulations were stopped. These data demonstrate that low-voltage-activated calcium currents are involved in epileptogenesis. Their enhancement in the dendrites will boost synaptic depolarization and result in enhanced calcium influx, which is critically dependent on the specific activation pattern.
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