Receptor-mediated calcium signals in astroglia: multiple receptors, common stores and all-or-nothing responses.
Calcium signals following activation of P2Y purinergic, alpha 1 adrenergic, and muscarinic cholinergic receptors were examined in individual astroglial cells. ATP, phenylephrine and carbachol, each increased intracellular calcium levels ([Ca2+]i) to similar amplitudes in the presence or absence of extracellular Ca2+. The dose-response relationship showed that less than an order of magnitude increase in ligand concentration led to maximal increase in [Ca2+]i from basal levels. Simultaneous application of multiple ligands did not produce additive effects on [Ca2+]i. These data suggested that different ligands released Ca2+ from common stores and that each of the ligands could cause maximal release. Application of a second ligand immediately after the first ligand produced an additional Ca2+ rise, suggesting that the Ca2+ stores were rapidly refilled and that receptor desensitization rather than Ca2+ depletion accounted for the rapid decline of the Ca2+ peak. Caged IP3 produced Ca2+ signals similar to those produced by ligands. For a given cell, both caged IP3 and ligands sometimes produced only one level of partial Ca2+ increases, suggesting the presence of a pool of high IP3-sensitive stores. Together, our results indicate that neuroligands tend to generate an all-or-nothing Ca2+ release from IP3 sensitive stores. The interactions between different receptor systems most likely occur at the level of IP3 accumulation.
Shao
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Y
Department of Pharmacology, University of North Carolina, Chapel Hill, USA.
McCarthy
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KD
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002451:Cell Compartmentation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008024:Ligands; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014741:Video Recording
D008024:Ligands; D017981:Receptors, Neurotransmitter; D010656:Phenylephrine; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D002217:Carbachol; D002118:Calcium