Tissue-specificity and alternative splicing of the na+-ca2+
exchanger isoforms ncx1, ncx2, and ncx3 in rat.
Quednau, Beate D., Debora A. Nicoll, and Kenneth D. Philipson.
Departments of Physiology and Medicine, and the Cardiovascular
Research Laboratories, University of California, Los Angeles, School
of Medicine, Los Angeles, CA 90095-1760
APStracts 3:0360C, 1996.
The gene coding for the Na+-Ca2+ exchanger, NCX1, is characterized by
a cluster of six exons (termed A, B, C, D, E, and F) coding for a
variable region in the C-terminus of the large intracellular loop of
the protein. Alternative splicing of these exons generates multiple
tissue-specific variants of NCX1. Using RT-PCR we analyzed eight
previously described and four new splicing isoforms of NCX1 in a wide
variety of tissues and cells. Exons A and B are mutually exclusive,
as shown in earlier studies, and splicing isoforms containing exon A
are preferentially expressed in heart, brain, and skeletal muscle,
whereas splicing variants with exon B are found in all rat tissues
except heart. The second and third isoforms of the Na+-Ca2+
exchanger, NCX2 and NCX3, both show a deletion of 37 amino acids in
the intracellular loop corresponding to parts of the variable region
of NCX1. We identified three splicing isoforms of NCX3 in brain and
skeletal muscle by RT-PCR. These splice variants are generated by
including either of two alternative exons equivalent to the NCX1
exons A or B, and by including or excluding a sequence equivalent to
the NCX1 exon C. We did not detect any alternative splicing of NCX2.
We examined selected tissues from neonatal and adult rats and found
developmental regulation for both NCX1 and NCX3 splicing isoforms in
skeletal muscle. Specific isoform patterns were also detected for
both NCX1 and NCX3 in cultured cortical neurons, astrocytes and
oligodendrocytes. We suggest a new terminology to distinguish the
different splice variants of individual NCX isoforms.
Received 5 August 1996; accepted in final form 29 October 1996.
APS Manuscript Number C443-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996