Inositol hexakisphosphate increases L-type Ca2+ channel activity by stimulation of adenylyl cyclase

Shao Nian Yang, Jia Yu, Georg W. Mayr, Fred Hofmann, Olof Larsson, Per Olof Berggren

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Inositol hexakisphosphate (InsP6) is a most abundant inositol polyphosphate that changes simultaneously with inositol 1,4,5-trisphosphate in depolarized neurons. However, the role of InsP6 in neuronal signaling is unknown. Mass assay reveals that the basal levels of InsP6 in several brain regions tested are similar. InsP6 mass is significantly elevated in activated brain neurons and lowered by inhibition of neuronal activity. Furthermore, the hippocampus is most sensitive to electrical challenge with regard to percentage accumulation of InsP6. In hippocampal neurons, InsP6 stimulates adenylyl cyclase (AC) without influencing cAMP phosphodiesterases, resulting in activation of protein kinase A (PKA) and thereby selective enhancement of voltage-gated L-type Ca2+ channel activity. This enhancement was abolished by preincubation with PKA and AC inhibitors. These data suggest that InsP6 increases L-type Ca2+ channel activity by facilitating phosphorylation of PKA phosphorylation sites. Thus, in hippocampal neurons, InsP6 serves as an important signal in modulation of voltage-gated L-type Ca2+ channel activity.

Original languageEnglish (US)
Pages (from-to)1753-1763
Number of pages11
JournalFASEB Journal
Volume15
Issue number10
DOIs
StatePublished - Aug 20 2001

Keywords

  • Adenylyl cyclase
  • Calcium channel
  • Hippocampus inositol polyphosphate
  • Protein kinase A

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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    Yang, S. N., Yu, J., Mayr, G. W., Hofmann, F., Larsson, O., & Berggren, P. O. (2001). Inositol hexakisphosphate increases L-type Ca2+ channel activity by stimulation of adenylyl cyclase. FASEB Journal, 15(10), 1753-1763. https://doi.org/10.1096/fj.00-0799com