Simply the Best?

Abstract

See related article, pages 864–872 Proteins encoded by best1 to -3 genes are implicated as molecular correlates of calcium-activated chloride channels in epithelia. In this issue of Circulation Research , Matchkov et al present compelling evidence that best-3 expression is essential for the generation of calcium-sensitive cGMP-dependent chloride channels in rat mesenteric artery.1 Chloride channels are enigmatic beasts. Numerous phenotypes exist, as determined by their mode of activation, channel kinetics, and pore properties, but the molecular identity has only really been identified for the voltage-dependent Cl− channels (CLCs) and the cAMP-dependent, cystic fibrosis transmembrane regulator (CFTR) channels. For the other types of Cl− channels, there is far less certainty about the molecular identity. Many candidates for the swelling-activated Cl− channel have been promulgated that ultimately have been repudiated.2 Similarly, the molecular identity of the Ca2+-gated Cl− channel, common to vascular smooth muscle cells, secretory cells, and cardiomyocytes remains to be elucidated.3 In this issue of Circulation Research , Matchkov et al suggest that we can add 1 more Cl− current to the list of identified species.1 Perversely, the calcium-sensitive cGMP-dependent Cl current, which is the focus of the work by Matchkov et al, is among the newest additions to the Cl− current family. This article …