title: Interleukin-1β activates an Src family kinase to stimulate the plasma membrane Ca2+ pump in hippocampal neurons.
abstract: The plasma membrane Ca(2+) ATPase (PMCA) plays a major role in clearing Ca(2+) from the neuronal cytoplasm. The cytoplasmic Ca(2+) clearance rate affects neuronal excitability, synaptic plasticity, and neurotransmission. Here, we examined the modulation of PMCA activity by PTKs in hippocampal neurons. PMCA-mediated Ca(2+) 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. Ca(2+) 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 Ca(2+) clearance, indicating that the kinase stimulates PMCA1. IL-1β accelerated Ca(2+) 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 Ca(2+) pump, decreasing the duration of Ca(2+) transients in hippocampal neurons.
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota.
authors: Biswarup
authors: B
authors: Ghosh
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota.
authors: Matthew V
authors: MV
authors: Green
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota.
authors: Kelly A
authors: KA
authors: Krogh
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota sathayer@umn.edu.
authors: Stanley A
authors: SA
authors: Thayer
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D019061:src-Family Kinases; D053499:Plasma Membrane Calcium-Transporting ATPases
keywords: Ca2+ signaling; IL-1β; PMCA; Src; Yes; hippocampal neuron