Gap junctional communication controls the overall endothelial calcium response to vasoactive agonists

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Abstract

Aims: A cytosolic calcium (Ca i2+) increase is an important activation signal for the endothelium. We investigated whether interendothelial spreading of the Ca 2+ signal via gap junctions (GJs) plays a role for the overall Ca i2+ increase in response to vasoactive agonists. Methods and results: In human umbilical vein endothelial cells (HUVECs), a Ca i2+ increase (Fura2) in response to histamine or ATP occurred initially only in about 30% of the cells (initially responding cells) reflecting the cell fraction expressing H 1 or purinergic receptors (FACS/immunohistochemistry). In the remaining adjacent cells, Ca i2+ increases occurred only after a delay of up to 5s. Blockade of GJ communication (meclofenamic acid and heptanol, or H 2O 2; verified by dye injection) did not affect responses in the initially responding cells but abolished the delayed Ca i2+ response of the remaining adjacent cells. The resulting reduction in the global endothelial Ca i2+ response significantly reduced the nitric oxide synthesis (assessed as cGMP levels). Similar Ca i2+ results were obtained in the endothelium of freshly isolated mouse (C57BL/6) aortas stimulated with ATP. The receptor-independent Ca i2+ response to ionomycin occurred simultaneously in all cells, regardless of GJ inhibition. In separate experiments, inhibition of the IP 3 receptor (xestospongin-C; 40, μmol/L) but not of the ryanodine receptor (ryanodine, 250 μmol/L) reduced the spread of the Ca i2+ signal into adjacent cells over longer distances. Conclusion: The global Ca i2+ response of the endothelium to agonists is determined decisively by the functionality of GJs, thus establishing a new role for GJs in controlling endothelial activity and vasomotor function. © The Author 2011.

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Kameritsch, P., Pogoda, K., Ritter, A., Münzing, S., & Pohl, U. (2012, March 1). Gap junctional communication controls the overall endothelial calcium response to vasoactive agonists. Cardiovascular Research. https://doi.org/10.1093/cvr/cvr345

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