title: Sodium influx plays a major role in the membrane depolarization induced by oxygen and glucose deprivation in rat striatal spiny neurons.
abstract: OBJECTIVE
  Striatal spiny neurons are selectively vulnerable to ischemia, but the ionic mechanisms underlying this selective vulnerability are unclear. Although a possible involvement of sodium and calcium ions has been postulated in the ischemia-induced damage of rat striatal neurons, the ischemia-induced ionic changes have never been analyzed in this neuronal subtype.
  
  
  METHODS
  We studied the effects of in vitro ischemia (oxygen and glucose deprivation) at the cellular level using intracellular recordings and microfluorometric measurements in a slice preparation. We also used various channel blockers and pharmacological compounds to characterize the ischemia-induced ionic conductances.
  
  
  RESULTS
  Spiny neurons responded to ischemia with a membrane depolarization/inward current that reversed at approximately -40 mV. This event was coupled with an increased membrane conductance. The simultaneous analysis of membrane potential changes and of variations in [Na+]i and [Ca2+]i levels showed that the ischemia-induced membrane depolarization was associated with an increase of [Na+]i and [Ca2+]i. The ischemia-induced membrane depolarization was not affected by tetrodotoxin or by glutamate receptor antagonists. Neither intracellular BAPTA, a Ca2+ chelator, nor incubation of the slices in low-Ca2+-containing solutions affected the ischemia-induced depolarization, whereas it was reduced by lowering the external Na+ concentration. High doses of blockers of ATP-dependent K+ channels increased the membrane depolarization observed in spiny neurons during ischemia.
  
  
  CONCLUSIONS
  Our findings show that, although the ischemia-induced membrane depolarization is coupled with a rise of [Na+]i and [Ca2+]i, only the Na+ influx plays a prominent role in this early electrophysiological event, whereas the increase of [Ca2+]i might be relevant for the delayed neuronal death. We also suggest that the activation of ATP-dependent K+ channels might counteract the ischemia-induced membrane depolarization.
authors.affiliation: Clinical Neurologica, Dip. Neuroscienze, Università di Roma Tor Vergata, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Calabresi
authors.forename: G A
authors.initials: GA
authors.lastname: Marfia
authors.forename: D
authors.initials: D
authors.lastname: Centonze
authors.forename: A
authors.initials: A
authors.lastname: Pisani
authors.forename: G
authors.initials: G
authors.lastname: Bernardi
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology; D002614:Chelating Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000098:blood supply / Q000166:cytology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D010100:Oxygen / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000502:physiology; D012964:Sodium / Q000378:metabolism* / Q000493:pharmacokinetics; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002614:Chelating Agents; D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D017470:Receptors, Glutamate; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D012964:Sodium; D008274:Magnesium; D005947:Glucose; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D010100:Oxygen; D005905:Glyburide; D002118:Calcium