Mechanisms of Neuronal Hyperexcitability Caused by Partial Inhibition of Na+-K+-ATPases in the Rat CA1 Hippocampal Region
| Autor: | Susanne E. Mason, Matthew F. Cuttle, Bradley E. Alger, Cyrille Vaillend |
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| Přispěvatelé: | Neurobiologie de l'apprentissage, de la mémoire et de la communication (NAMC), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, University of Maryland School of Medicine |
| Rok vydání: | 2002 |
| Předmět: |
Male
MESH: Hippocampus Physiology Postsynaptic Current [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology MESH: Neurons Action Potentials MESH: Rats Sprague-Dawley MESH: gamma-Aminobutyric Acid Hippocampus Synaptic Transmission MESH: Differential Threshold Rats Sprague-Dawley MESH: Osmolar Concentration 0302 clinical medicine Glutamates MESH: Ouabain MESH: Presynaptic Terminals MESH: Animals Ouabain MESH: Action Potentials gamma-Aminobutyric Acid MESH: Sodium-Potassium-Exchanging ATPase Neurons 0303 health sciences MESH: Electrophysiology [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior Chemistry Pyramidal Cells General Neuroscience [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences Depolarization Hyperpolarization (biology) Electrophysiology MESH: Epilepsy Excitatory postsynaptic potential MESH: Rest Sodium-Potassium-Exchanging ATPase MESH: Rats Rest Presynaptic Terminals Differential Threshold Neurotransmission Inhibitory postsynaptic potential 03 medical and health sciences Bursting MESH: Glutamates MESH: Synaptic Transmission Animals MESH: Excitatory Postsynaptic Potentials 030304 developmental biology Epilepsy Osmolar Concentration Excitatory Postsynaptic Potentials MESH: Pyramidal Cells MESH: Male Rats nervous system MESH: Potassium Potassium Biophysics Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurophysiology Journal of Neurophysiology, American Physiological Society, 2002, 88 (6), pp.2963-2978. ⟨10.1152/jn.00244.2002⟩ |
| ISSN: | 1522-1598 0022-3077 |
| DOI: | 10.1152/jn.00244.2002 |
| Popis: | Extra- and intracellular records were made from rat acute hippocampal slices to examine the effects of partial inhibition of Na+-K+-ATPases (Na+-K+pumps) on neuronal hyperexcitability. Bath application of the low-affinity cardiac glycoside, dihydroouabain (DHO), reversibly induced interictal-like epileptiform bursting activity in the CA1 region. Burst-firing was correlated with inhibition of the pumps, which was assayed by changes in [K+]ouptake rates measured with K+-ion-sensitive microelectrodes. Large increases in resting [K+]odid not occur. DHO induced a transient depolarization (5–6 mV) followed by a long-lasting hyperpolarization (∼6 mV) in CA1 pyramidal neurons, which was accompanied by a 30% decrease in resting input resistance. Block of an electrogenic pump current could explain the depolarization but not the hyperpolarization of the membrane. Increasing [K+]ofrom 3 to 5.5 mM minimized these transient shifts in passive membrane properties without preventing DHO-induced hyperexcitability. DHO decreased synaptic transmission, but increased the coupling between excitatory postsynaptic potentials and spike firing (E-S coupling). Monosynaptic inhibitory postsynaptic potential (IPSP) amplitudes declined to ∼25% of control at the peak of bursting activity; however, miniature TTX-resistant inhibitory postsynaptic current amplitudes were unaffected. DHO also reduced the initial slope of the intracellular excitatory postsynaptic potential (EPSP) to ∼40% of control. The conductances of pharmacologically isolated IPSPs and EPSPs in high-Ca/high-Mg-containing saline were also reduced by DHO by ∼50%. The extracellular fiber volley amplitude was reduced by 15–20%, suggesting that the decrease in neurotransmission was partly due to a reduction in presynaptic fiber excitability. DHO enhanced a late depolarizing potential that was superimposed on the EPSP and could obscure it. This potential was not blocked by antagonists of NMDA receptors, and blockade of NMDA, mGlu, or GABAAreceptors did not affect burst firing. The late depolarizing component enabled the pyramidal cells to reach spike threshold without changing the actual voltage threshold for firing. We conclude that reduced GABAergic potentials and enhanced E-S coupling are the primary mechanisms underlying the hyperexcitability associated with impaired Na+-K+pump activity. |
| Databáze: | OpenAIRE |
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