Abstract
MANY hormones, neurotransmitters and growth factors evoke in their target cells oscillations in the free internal Ca2+ concentration ([Ca2+]i) (ref. 1). In electrically non-excitable cells these fluctuations are due to periodic release of Ca2+ from intracellular reservoirs1,2, stimulated by the internal messenger inositol trisphosphate (InsP3) (refs 2–4). Most models at present invoke fluctuating levels of InsP3 as a key component in generating the oscillations in [Ca2+]i (refs 5 and 6). InsP3 injected into intact cells evokes irregular and transient oscillatory Ca2+-dependent current responses7–9, but the intracellular InsP3 concentration is not constant in such experiments. Here we monitor changes in [Ca2+i by measuring Ca2+-activated Cl- current in single internally perfused mouse pancreatic acinar cells4,10–12and show that acetylcholine (ACh), acting through muscarinic receptors, evokes regular and repetitive current pulses which are mimicked by InsP3 applied through a patch pipette13. To exclude the possibility that InsP3is periodically phosphorylated14 or degraded, we replaced it by the non-metabolizable InsP3 analogue inositol trisphosphorothioate (InsPS3)9,15,16, which also evokes regular pulses of Ca2+-activated Cl- current. These effects are independent of external Ca2+, but abolished by high intracellular concentrations of a Ca2+-chelator. We conclude that repetitive pulses of intracellular Ca2+release occur even when the concentration of InsP3 is constant.
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Wakui, M., Potter, B. & Petersen, O. Pulsatile intracellular calcium release does not depend on fluctuations in inositol trisphosphate concentration. Nature 339, 317–320 (1989). https://doi.org/10.1038/339317a0
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DOI: https://doi.org/10.1038/339317a0
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