Bradykinin inhibits M current via phospholipase C and Ca 2+ release from IP 3 -sensitive Ca 2+ stores in rat sympathetic neurons
| Autor: | Bertil Hille, Duk Su Koh, Humberto Cruzblanca |
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| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Sympathetic Nervous System Thapsigargin Bradykinin Inositol 1 4 5-Trisphosphate Biology Calcium in biology Rats Sprague-Dawley chemistry.chemical_compound Internal medicine M current Muscarinic acetylcholine receptor medicine Animals Bradykinin receptor Neurons Multidisciplinary Phospholipase C Biological Transport Biological Sciences Receptors Muscarinic Rats Cell biology Endocrinology chemistry Type C Phospholipases Second messenger system Calcium Calcium Channels Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 95:7151-7156 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.95.12.7151 |
| Popis: | A variety of intracellular signaling pathways can modulate the properties of voltage-gated ion channels. Some of them are well characterized. However, the diffusible second messenger mediating suppression of M current via G protein-coupled receptors has not been identified. In superior cervical ganglion neurons, we find that the signaling pathways underlying M current inhibition by B 2 bradykinin and M 1 muscarinic receptors respond very differently to inhibitors. The bradykinin pathway was suppressed by the phospholipase C inhibitor U-73122, by blocking the IP 3 receptor with pentosan polysulfate or heparin, and by buffering intracellular calcium, and it was occluded by allowing IP 3 to diffuse into the cytoplasm via a patch pipette. By contrast, the muscarinic pathway was not disrupted by any of these treatments. The addition of bradykinin was accompanied by a [Ca 2+ ] i rise with a similar onset and time to peak as the inhibition of M current. The M current inhibition and the rise of [Ca 2+ ] i were blocked by depletion of Ca 2+ internal stores by thapsigargin. We conclude that bradykinin receptors inhibit M current of sympathetic neurons by activating phospholipase C and releasing Ca 2+ from IP 3 -sensitive Ca 2+ stores, whereas muscarinic receptors do not use the phospholipase C pathway to inhibit M current channels. |
| Databáze: | OpenAIRE |
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