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

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 E-2 (PGE(2)) in osteocytes. However, we have found that Cx43-null osteoblasts have unaltered, mechanically induced PGE(2) release and ATP-induced YoPro dye uptake. In contrast, PGE(2) release in response to fluid shear stress is abolished in P2X(7) receptor (P2X(7)R)-null osteoblasts, and ATP-induced dye uptake is attenuated following treatment of wild-type cells with a P2X(7)R or Pannexin1 (Panx1) channel blocker. These data indicate that Panx1 channels, in concert with P2X(7)R, likely form a molecular complex that performs the hemichannel function in osteoblast mechanosignaling.