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ATP Release Via Connexin Hemichannels Controls Intercellular Propagation of Ca2+ Waves in Corneal Endothelial Cells

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Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function

Abstract

Intercellular communication (IC) is essential for coordinating cellular activity in multi-cellular organisms, and plays a role in many physiological and pathological processes. Direct IC between adjacent cells is mainly mediated by gap junctions, whereas paracrine signaling provides an indirect pathway for IC between neighboring cells. Purinergic mediators are important messengers in this paracrine signaling, and recent evidence shows that connexin and pannexin hemichannels form an important release pathway for ATP involved in purinergic IC.

We have investigated the properties of IC via Ca2+ waves evoked by mechanical stimulation of a single cell in monolayers of bovine corneal endothelial cells (BCEC). We have demonstrated that both gap junctions and paracrine IC are involved in the Ca2+ wave propagation, and that purinergic paracrine signaling is the main component of IC in BCEC. Furthermore, our results demonstrate that connexin43 hemichannels provide the pathway for ATP release. Our experiments show that the paracrine IC is strongly reduced in the presence of inflammatory agents, such as histamine and thrombin, that enhance actomyosin contraction. The effect of these agents is due to inhibition of hemichannel-mediated ATP release. This effect of thrombin can be precluded by preincubation of the cells with adenosine. Possible roles of paracrine IC to “bystander” and “good Samaritan” effects are discussed.

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Acknowledgments

Supported by FWO-Vlaanderen G.0218.03, GOA/2004/07, IAP program 5/05 (BH and JV) and NIH grant R21-EY019119 and Faculty Research Grant, VP of Research, IU Bloomington, IN (SPS).

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  1. Laboratory of Molecular and Cellular Signaling, Department of Molecular Cell Biology, KULeuven, Campus Gasthuisberg O&N1, B-3000, Leuven, Belgium

    Raf Ponsaerts, Catheleyne D’hondt, Geert Bultynck, Johan Vereecke & Bernard Himpens

  2. Physiology lab, KULeuven, subfaculty Kortrijk, E. Sabbelaan 53, B-8500, Kortrijk, Belgium

    Priya Gomes

  3. Indiana University, School of Optometry, Bloomington, IN, 47405, USA

    Sangly P. Srinivas

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  1. Raf Ponsaerts
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Correspondence to Johan Vereecke .

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  1. Dept. Pediatrics, Pediatric Clinical Services, University of Colorado, Denver, East 19th Avenue 12700, Aurora, 80045, USA

    Evgenia Gerasimovskaya

  2. Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline Ave. 99, Boston, 02215, USA

    Elzbieta Kaczmarek

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Ponsaerts, R. et al. (2010). ATP Release Via Connexin Hemichannels Controls Intercellular Propagation of Ca2+ Waves in Corneal Endothelial Cells. In: Gerasimovskaya, E., Kaczmarek, E. (eds) Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3435-9_10

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