Regional differences in expression of transcripts for Na+/Ca2+ exchanger isoforms in rat brain.

The Na+/Ca2+ exchanger has a primary role in maintaining intraneuronal Ca2+ homeostasis. There are three distinct Na+/Ca2+ exchanger isoforms cloned from rat brain, NCX1, NCX2 and NCX3, which are the products of three different genes. In the present study, isoform expression in different regions of rat brain was determined by using reverse transcription PCR (RT-PCR) and Northern analysis. RT-PCR detected all three Na+/Ca2+ exchanger isoforms in each region studied (brainstem/spinal cord, cerebellum, cerebral cortex, striatum/septum and hippocampus). Northern analysis was performed to determine the steady-state mRNA levels of each isoform. NCX1 had two transcripts, 14 and 7 kb, and the 7-kb transcript was predominant in brainstem/spinal cord, cerebellum and hippocampus. NCX2 expression (4.8-kb transcript) was an order of magnitude higher than NCX1 or NCX3 expression in all the five areas except brainstem/spinal cord where the 4.8-kb transcript was nearly absent. The third isoform (NCX3) had two transcripts, one was 6 kb and the other was 4 kb. The 6-kb transcript was predominant in brainstem/spinal cord and cerebellum. The results suggest that Na+/Ca2+ exchanger isoforms are expressed ubiquitously in rat brain but that each isoform shows a unique distribution within the brain. The exchanger probably participates in the regulation of intracellular calcium homeostasis in a wide range of cell types within the brain. Furthermore, individual cells may contain more than one type of exchanger isoform with distinct subcellular distributions.