Antisense oligonucleotide suppression of Na+/Ca2+ exchanger activity in primary neurons from rat brain

An antisense (AS) oligodeoxynucleotide based on a conserved sequence in the three isoforms of the Na+/Ca2+ exchanger (NCX) was used to decrease expres sion of this Ca2+ transporter in primary neuronal cultures. Two AS oligo ap plications decreased NCX activity by similar to 40% within 12-24 h, and nei ther sense (S) or missense (MS) oligos altered NCX activity. The reduced NC X expression was confirmed by immunoblots and enzyme-linked immunosorbent a ssays (ELISAs). Resting [Ca2+](i) levels were 20% higher in AS-treated neur ons and showed a slower return to baseline levels following activation of C a2+ influx by N-methyl-D-aspartate (NMDA). These results suggest that NCX p lays a significant role in maintaining neuronal Ca2+ homeostasis and in res toring baseline Ca2+ levels following depolarization. (C) 2000 Elsevier Sci ence Ireland Ltd. All rights reserved.