<p>Communication between neuronal and non-neuronal is called volume transmission when the released neurotransmitter (NT) acts via diffusion and affects several target cells. Both the neurosecretory and postsynaptic cell responses are linked to [Ca<sup>2+</sup>]<sub>i</sub> elevations. </p><p>In the present thesis the role of pre-and postsynaptic Ca<sup>2+</sup> elevations has been investigated in the reconstituted "synapse" model comprised of NGF-differentiated PC12 and HEL cells as well as in SH-SY5Y neuroblastoma cells. In PC12 cells, both 70mM K<sup>+</sup> and nicotine triggered NT release, which could be detected as a secondary [Ca<sup>2+</sup>]<sub>i</sub> increase in surrounding HEL cells. Both secretagogues shared the same voltage-dependent Ca<sup>2+</sup> influx pathway as judged from the pharmacological profile blockers of voltage-gated Ca<sup>2+</sup> channels. The coupling of electrical responses to the activation of Ca<sup>2+</sup> signaling via muscarinic receptors in SH-SY5Y cells was also studied. These data revealed that depolarization caused a considerable potentiation of the muscarinic Ca<sup>2+</sup> response. The potentiated Ca<sup>2+</sup> increase was mainly dependent on the enhanced Ca<sup>2+</sup> influx and to a lesser extent on [Ca<sup>2+</sup>]<sub>i</sub> release from intracellular stores. A phospholipase C (PLC) activator, m-3M3FBS was used to further study the role of G-protein coupled receptor (GPCR)-coupled Ca<sup>2+</sup> signaling. However, it was found that m-3M3FBS instead triggered [Ca<sup>2+</sup>]<sub>i</sub> elevations independently of PLC activation. </p><p>In conclusion, the results indicate that the magnitude of NT release from PC12 cells is sufficient to cause a robust activation of neighboring target cells. Postsynaptic muscarinic signaling is amplified due to integration of electrical excitation and GPCR signaling. The PLC activator, m-3M3FBS is not suitable for studies of PLC-mediated signals in intact cells.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-4300 |
| Date | January 2004 |
| Creators | Krjukova, Jelena |
| Publisher | Uppsala University, Department of Neuroscience, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1361 |
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