Transcript distribution of plasma membrane Ca2+ pump isoforms and splice variants in the human brain

David A. Zacharias, Stephen J. Dalrymple, Emanuel E. Strehler

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Plasma membrane calcium pumps (PMCAs) play a major role in the maintenance and fine regulation of the intracellular Ca2+ concentration. Fourteen subregions of the normal human brain were carefully dissected and analyzed by reverse transcriptase-polymerase chain reaction for the distribution of rnRNAs corresponding to the four known PMCA genes as well as their alternative splicing products at two previously defined 'hotspots' A and C. All PMCA genes were found to be expressed in every brain subregion; however, consistent differences were found in the distribution of alternative splice options. The four cortical regions and hippocampus were characterized by the relative preference of variants that include an entire exon at site C and lead to the expression of isoforms of the a-type. Inferior olive and olfactory bulb showed a relative preponderance of the b-form 'default' types of alternative splicing at site C, and a decrease or even the lack of 'differentiated' forms such as variants la and 1c. At the N-terminal splice site A, the default x-type variants were predominant in all brain regions for PMCA 1, 3, and 4. By contrast, the pattern of PMCA2 variants was the most variable, ranging from the presence of the entire set of 2x, 2w, and 2z forms in inferior olive to the almost exclusive presence of form 2z (excluding all alternatively spliced sequences) in the four cortical regions, caudate, and hippocampus. Regional differences in the PMCA splice type distribution in normal human brain may correlate with different demands on the regulation of the set-point resting Ca2+ levels in these areas. Changes in these patterns may correlate with altered physiological states of the affected regions and/or reflect an (early) sign of Ca 2+ dyshomeostasis characteristic of many neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalMolecular Brain Research
Volume28
Issue number2
DOIs
StatePublished - Feb 1995

Keywords

  • Alternative splicing
  • Calcium
  • Calcium ATPase
  • Calcium homeostasis
  • Human brain
  • Polymerase chain reaction
  • Tissue distribution

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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