Ca 2+ and Inositol 1,4,5-Trisphosphate–Mediated Signaling Across the Myoendothelial Junction
| Autor: | Brian R. Duling, Susan I. Ramos, Brant E. Isakson |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Thapsigargin Physiology Cell Communication Inositol 1 4 5-Trisphosphate Biology Cell junction Muscle Smooth Vascular Calcium in biology Mice chemistry.chemical_compound BAPTA Internal medicine medicine Animals Inositol Calcium Signaling Cells Cultured Calcium signaling Gap Junctions Cell biology B vitamins Endocrinology chemistry Second messenger system Calcium Endothelium Vascular Cardiology and Cardiovascular Medicine |
| Zdroj: | Circulation Research. 100:246-254 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/01.res.0000257744.23795.93 |
| Popis: | Second messenger signaling between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) is poorly understood, but intracellular Ca 2+ concentrations ([Ca 2+ ] i ) in the 2 cells are coordinated, possibly through gap junctions at the myoendothelial junction. To study heterocellular calcium signaling, we used a vascular cell coculture model composed of monolayers of ECs and VSMCs. Stimulation of either cell type leads to an increase in [Ca 2+ ] i in the stimulated cell and a secondary increase in [Ca 2+ ] i in the other cell type that was blocked by gap junction inhibitors. To determine which second messengers are involved, we initially depleted Ca 2+ stores in the endoplasmic reticulum Ca 2+ with thapsigargin in ECs or VSMCs, but this had no effect on heterocellular calcium signaling. Alternatively, we loaded ECs or VSMCs with 1,2-bis(2-aminophenoxy)ethane- N , N , N ′, N ′-tetraacetic acid (BAPTA) to buffer changes in [Ca 2+ ] i . BAPTA loading of ECs inhibited agonist-induced increases in intracellular calcium concentration ([Ca 2+ ] i ), in both ECs and VSMCs. In contrast, BAPTA loading of the VSMCs blunted the VSMC response but did not alter the secondary increase in EC [Ca 2+ ] i . Xestospongin C (an inositol 1,4,5-trisphosphate receptor inhibitor) had no effect on the secondary Ca 2+ response, but when xestospongin C or thapsigargin was loaded into ECs and BAPTA into VSMCs, intercellular Ca 2+ signaling was completely blocked. We conclude that 1,4,5-trisphosphate and Ca 2+ originating in the VSMCs induces the secondary increase in EC [Ca 2+ ] i but stimulation of the ECs generates a Ca 2+ dependent response in the VSMCs. |
| Databáze: | OpenAIRE |
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