Connexins 40 and 43 form heteromeric gap junction channels in vascular smooth muscle cells

Abstract

Gap junction channels connect the cytoplasms of adjacent cells and provide a pathway for the exchange of materials between cells. The nature of the materials exchanged is determined by the biophysical characteristics of the channels. The functional gap junction channel is composed of paired hemichannels (connexons) from each cell. Connexons are hexamers of protein subunits called connexins (Cx). Of the 15 connexin genes found in the mammalian genome, the products of only two, Cx40 and Cx43 have been localized in vascular smooth muscle cells (SMC) (1;2). We have been interested in identifying the role of gap junctions in cardiac rhythmic activity and vascular function. Like many other cell types, mammalian heart and blood vessels express multiple gap junction connexins (3). These connexins may form heteromeric channels. A7r5 cells, a cell line derived from embryonic rat aortic smooth muscle cells, provide a good model because they express both connexins 40 and 43. From the previous studies in this laboratory, Moore and Burt reported the presence of channels with a wide range of unitary conductance with major peaks at 75, 110 and 145 pS. One explanation for the wide range of unitary conductance could be the presence of heteromeric Cx40 and Cx43 channels. Thus, the goal of this study was to investigate gating behaviors of gap junction channels in A7r5 cells to determine whether heteromeric Cx40/43 channels are formed. I will demonstrate that Cx40 and Cx43 form heteromeric channels with unique unitary conductances, voltage-dependent gating properties and enhanced sensitivity to halothane induced closure.