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Connexin43 and Pannexin1 Channels in Osteoblasts: Who Is the “Hemichannel”?

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Abstract

Osteoblasts sense and respond to mechanical stimuli in a process involving influx and release of large ions and signaling molecules. Unapposed gap junction hemichannels formed of connexin43 (Cx43) have been proposed as a major route for such exchange, in particular for release of ATP and prostaglandin E2 (PGE2) in osteocytes. However, we have found that Cx43-null osteoblasts have unaltered, mechanically induced PGE2 release and ATP-induced YoPro dye uptake. In contrast, PGE2 release in response to fluid shear stress is abolished in P2X7 receptor (P2X7R)–null osteoblasts, and ATP-induced dye uptake is attenuated following treatment of wild-type cells with a P2X7R or Pannexin1 (Panx1) channel blocker. These data indicate that Panx1 channels, in concert with P2X7R, likely form a molecular complex that performs the hemichannel function in osteoblast mechanosignaling.

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Acknowledgments

This work was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease [Grants DK091466 (to M.M.T.), DK081435 (to S.O.S.)] and the National Institute of Arthritis and Musculoskeletal and Skin Diseases [Grant AR057139 (to D.C.S)].

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Mia M. Thi

  2. Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Mia M. Thi, Sylvia O. Suadicani & David C. Spray

  3. Department of Biology, The City College of New York, New York, NY, 10031, USA

    Shalena Islam

  4. Department of Urology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Sylvia O. Suadicani

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  1. Mia M. Thi
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Correspondence to Mia M. Thi.

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Thi, M.M., Islam, S., Suadicani, S.O. et al. Connexin43 and Pannexin1 Channels in Osteoblasts: Who Is the “Hemichannel”?. J Membrane Biol 245, 401–409 (2012). https://doi.org/10.1007/s00232-012-9462-2

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