Pharmacological Inhibition of the Na + /Ca 2+ Exchanger Enhances Depolarizations Induced by Oxygen/Glucose Deprivation but Not Responses to Excitatory Amino Acids in Rat Striatal Neurons

Abstract

Background and Purpose—Neuronal Na+/Ca2+ exchanger plays a relevant role in maintaining intracellular Ca2+ and Na+ levels under physiological and pathological conditions. However, the role of this exchanger in excitotoxicity and ischemia-induced neuronal injury is still controversial and has never been studied in the same neuronal subtypes. Methods—We investigated the effects of bepridil and 3′,4′-dichlorobenzamil (DCB), 2 blockers of the Na+/Ca2+ exchanger, in rat striatal spiny neurons by utilizing intracellular recordings in brain slice preparations to compare the action of these drugs on the membrane potential changes induced either by oxygen and glucose deprivation (OGD) or by excitatory amino acids (EAAs). Results—Bepridil (3 to 100 μmol/L) and DCB (3 to 100 μmol/L) caused a dose-dependent enhancement of the OGD-induced depolarization measured in striatal neurons. The EC50 values for these effects were 31 μmol/L and 29 μmol/L, respectively. At these concentrations neither bepridil nor DCB altered th...