Intercellular calcium waves in primary cultured rat mesenteric smooth muscle cells are mediated by Connexin43

Abstract

Intercellular Ca^{2 +} wave propagation between vascular smooth muscle cells (SMCs) is associated with the propagation of contraction along the vessel. Here, we characterize the involvement of gap junctions (GJs) in Ca^{2 +} wave propagation between SMCs at the cellular level. Gap junctional communication was assessed by the propagation of intercellular Ca^{2 +} waves and the transfer of Lucifer Yellow in A7r5 cells, primary rat mesenteric SMCs (pSMCs), and 6B5N cells, a clone of A7r5 cells expressing higher connexin43 (Cx43) to Cx40 ratio. Mechanical stimulation induced an intracellular Ca^{2 +} wave in pSMC and 6B5N cells that propagated to neighboring cells, whereas Ca^{2 +} waves in A7r5 cells failed to progress to neighboring cells. We demonstrate that Cx43 forms the functional GJs that are involved in mediating intercellular Ca^{2 +} waves and that co-expression of Cx40 with Cx43, depending on their expression ratio, may interfere with Cx43 GJ formation, thus altering junctional communication.

Keywords::

• connexins
• gap junction
• calcium waves

Acknowledgments

We thank Dr. Lysianne Follonier Castella and Dr. François-Xavier Boittin for valuable suggestions and expert help. We are grateful to Dr. Aurélie Formey for help with the preparation of the primary culture, and Josiane Smith-Clerc for excellent technical assistance. This work was supported by the Swiss National Science Foundation, Grants FN 310000-114097 and 310300-127122 (J.-J. Meister), FN 31003A-138528/1 (J.-A. Haefliger) and National Institutes of Health grant RO1HL58732 (J. M. Burt). JAH was also supported by the Novartis Foundation.

Conflict of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.