On the mechanisms underlying hypoxia-induced membrane depolarization in striatal neurons. 1995

P Calabresi, and A Pisani, and N B Mercuri, and G Bernardi
Clinica Neurologica, Università di Roma Tor Vergata, Italy.

Clinical and experimental evidence has shown that the striatal neurons are particularly vulnerable to hypoxia and ischaemia. An excessive excitatory action of glutamate, released by the corticostriatal terminals, has been implicated in this peculiar vulnerability of striatal neurons. We have studied the effects of hypoxia on the membrane properties of striatal neurons intracellularly recorded from a corticostriatal slice preparation. Brief (2-10 min) periods of hypoxia produced reversible membrane depolarizations. During the initial phase of the hypoxia-induced depolarization the frequency of action potential discharge was transiently increased; 2-3 min after the onset of hypoxia the firing activity was fully abolished. Brief periods of hypoxia also caused a reversible reduction of the amplitude of the excitatory postsynaptic potentials (EPSPs) evoked by cortical stimulation. Longer period of hypoxia (12-20 min) produced irreversible membrane depolarizations. In voltage-clamp experiments hypoxia caused an inward current coupled with an increased membrane conductance. Tetrodotoxin (TTX) or low calcium (Ca2+)-high magnesium containing solutions blocked synaptic transmission, but they did not reduce the hypoxia-induced electrical changes. Antagonists of excitatory amino acid receptors failed to affect the electrical effects caused by oxygen deprivation. Hypoxia-induced inward currents were reduced either by the potassium (K+) channel blockers, barium and tetraethyl ammonium (TEA) cations, or by lowering external sodium (Na+) concentration. Blockade of ATP-dependent Na(+)-K+ pump by both ouabain and strophanthidin enhanced hypoxia-induced membrane depolarization/inward current. Our findings indicate that the release of excitatory amino acids does not seem to be required for the acute hypoxia-induced electrical changes in striatal neurons. Moreover, TTX-resistant Na+ influx and K+ currents seem to play an important role in the generation of hypoxia-induced electrical changes. These data also suggest that the selective vulnerability of striatal neurons to oxygen deprivation may be caused by their peculiar sensitivity to energy metabolism failure.

UI MeSH Term Description Entries
D008297 Male Males
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002534 Hypoxia, Brain A reduction in brain oxygen supply due to ANOXEMIA (a reduced amount of oxygen being carried in the blood by HEMOGLOBIN), or to a restriction of the blood supply to the brain, or both. Severe hypoxia is referred to as anoxia and is a relatively common cause of injury to the central nervous system. Prolonged brain anoxia may lead to BRAIN DEATH or a PERSISTENT VEGETATIVE STATE. Histologically, this condition is characterized by neuronal loss which is most prominent in the HIPPOCAMPUS; GLOBUS PALLIDUS; CEREBELLUM; and inferior olives. Anoxia, Brain,Anoxic Encephalopathy,Brain Hypoxia,Cerebral Anoxia,Encephalopathy, Hypoxic,Hypoxic Encephalopathy,Anoxia, Cerebral,Anoxic Brain Damage,Brain Anoxia,Cerebral Hypoxia,Hypoxia, Cerebral,Hypoxic Brain Damage,Anoxic Encephalopathies,Brain Damage, Anoxic,Brain Damage, Hypoxic,Damage, Anoxic Brain,Damage, Hypoxic Brain,Encephalopathies, Anoxic,Encephalopathies, Hypoxic,Encephalopathy, Anoxic,Hypoxic Encephalopathies
D002545 Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION. Cerebral Ischemia,Ischemic Encephalopathy,Encephalopathy, Ischemic,Ischemia, Cerebral,Brain Ischemias,Cerebral Ischemias,Ischemia, Brain,Ischemias, Cerebral,Ischemic Encephalopathies
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004553 Electric Conductivity The ability of a substrate to allow the passage of ELECTRONS. Electrical Conductivity,Conductivity, Electric,Conductivity, Electrical
D000254 Sodium-Potassium-Exchanging ATPase An enzyme that catalyzes the active transport system of sodium and potassium ions across the cell wall. Sodium and potassium ions are closely coupled with membrane ATPase which undergoes phosphorylation and dephosphorylation, thereby providing energy for transport of these ions against concentration gradients. ATPase, Sodium, Potassium,Adenosinetriphosphatase, Sodium, Potassium,Na(+)-K(+)-Exchanging ATPase,Na(+)-K(+)-Transporting ATPase,Potassium Pump,Sodium Pump,Sodium, Potassium ATPase,Sodium, Potassium Adenosinetriphosphatase,Sodium-Potassium Pump,Adenosine Triphosphatase, Sodium, Potassium,Na(+) K(+)-Transporting ATPase,Sodium, Potassium Adenosine Triphosphatase,ATPase Sodium, Potassium,ATPase, Sodium-Potassium-Exchanging,Adenosinetriphosphatase Sodium, Potassium,Pump, Potassium,Pump, Sodium,Pump, Sodium-Potassium,Sodium Potassium Exchanging ATPase,Sodium Potassium Pump
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013757 Tetraethylammonium Compounds Quaternary ammonium compounds that consist of an ammonium cation where the central nitrogen atom is bonded to four ethyl groups. Tetramon,Tetrylammonium,Compounds, Tetraethylammonium

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