Sodium influx plays a major role in the membrane depolarization induced by oxygen and glucose deprivation in rat striatal spiny neurons.

Abstract

BACKGROUND AND PURPOSE:

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: P Calabresi, G A Marfia, D Centonze, A Pisani, G Bernardi
• Journal: Stroke (Stroke) Vol. 30 Issue 1 Pg. 171-9 (Jan 1999) ISSN: 0039-2499 [Print] United States
• PMID: 9880406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Calcium Channels
• Chelating Agents
• Hypoglycemic Agents
• Potassium Channel Blockers
• Potassium Channels
• Receptors, Glutamate
• Sodium Channel Blockers
• Sodium Channels
• Tetrodotoxin
• Egtazic Acid
• Adenosine Triphosphate
• Tolbutamide
• Sodium
• Magnesium
• Glucose
• 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
• Oxygen
• Glyburide
• Calcium

Topics

• Adenosine Triphosphate (physiology)
• Animals
• Brain Ischemia (metabolism)
• Calcium (metabolism, pharmacology)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels (physiology)
• Cerebral Cortex (blood supply, cytology)
• Chelating Agents (pharmacology)
• Corpus Striatum (blood supply, cytology)
• Egtazic Acid (analogs & derivatives, pharmacology)
• Glucose (pharmacology)
• Glyburide (pharmacology)
• Hypoglycemic Agents (pharmacology)
• Magnesium (pharmacology)
• Membrane Potentials (drug effects, physiology)
• Neurons (chemistry, drug effects, physiology)
• Organ Culture Techniques
• Oxygen (pharmacology)
• Patch-Clamp Techniques
• Potassium Channel Blockers
• Potassium Channels (physiology)
• Rats
• Rats, Wistar
• Receptors, Glutamate (physiology)
• Sodium (metabolism, pharmacokinetics)
• Sodium Channel Blockers
• Sodium Channels (physiology)
• Tetrodotoxin (pharmacology)
• Tolbutamide (pharmacology)