Interleukin-1β activates an Src family kinase to stimulate the plasma membrane Ca2+ pump in hippocampal neurons

Biswarup Ghosh, Matthew V. Green, Kelly A. Krogh, Stanley A Thayer

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The plasma membrane Ca2+ ATPase (PMCA) plays a major role in clearing Ca2+ from the neuronal cytoplasm. The cytoplasmic Ca2+ clearance rate affects neuronal excitability, synaptic plasticity, and neurotransmission. Here, we examined the modulation of PMCA activity by PTKs in hippocampal neurons. PMCA-mediated Ca2+ clearance slowed in the presence of pyrazolopyrimidine 2, an inhibitor of Src family kinases (SFKs), and accelerated in the presence of C2-ceramide, an activator of PTKs. Ca2+ clearance kinetics were attenuated in cells expressing a dominant-negative Src mutant, suggesting that the pump is tonically stimulated by a PTK. Tonic stimulation was reduced in hippocampal neurons expressing short hairpin (sh)RNA directed to mRNA for Yes. shRNA-mediated knockdown of PMCA isoform 1 (PMCA1) removed tonic stimulation of Ca2+ clearance, indicating that the kinase stimulates PMCA1. IL-1β accelerated Ca2+ clearance in a manner blocked by an IL-1β receptor antagonist or by an inhibitor of neutral sphingomyelinase, the enzyme that produces ceramide. Thus IL-1β activates an SFK to stimulate the plasma membrane Ca2+ pump, decreasing the duration of Ca2+ transients in hippocampal neurons.

Original languageEnglish (US)
Pages (from-to)1875-1885
Number of pages11
JournalJournal of neurophysiology
Volume115
Issue number4
DOIs
StatePublished - Apr 1 2016

Bibliographical note

Funding Information:
Support for this work was provided by the National Institute on Drug Abuse (Grant DA07304).

Publisher Copyright:
© 2016 the American Physiological Society.

Keywords

  • Ca signaling
  • Hippocampal neuron
  • IL-1β
  • PMCA
  • Src
  • Yes

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