The 57th Annual Meeting and Symposium of the Society of General Physiologists The Biology of Chloride

If for no other reason than the need to maintain elec-troneutrality, anions are the equals of cations, and chloride channel dysfunctions underlie not only in cystic fi-brosis but a host of other diseases. Nevertheless, anions often appear to take the backstage in discussions of membrane transport and ionic homeostasis. Recently, however, they got equal time at the 57 th Annual Meet-ganized the symposium on Biology of Chloride, which highlighted the recent progress that has taken place in understanding the physiological importance of cellular Cl Ϫ homeostasis and transport. With 196 participants, and 120 invited and poster presentations covering a broad range of topics. Though the topic was profoundly negative, the meeting was very lively. The meeting's Keynote Speaker, Thomas J. Jentsch (Universität Hamburg, Germany), set the standard with a masterful overview of the mammalian ClC family of chloride channels (or putative chloride channels), which are involved in both plasma membrane and or-ganellar Cl Ϫ movement (Fig. 1). The ClC proteins are conserved from bacteria to man and, as is the case for many membrane proteins, atomic resolution structures are known only for the bacterial homologues The membrane-spanning proteins are dimers of subunits with 16 (partial) transmembrane segments; each subunit forms an independent channel (or per-meation path). General features of ClC channels are their selectivity for Cl Ϫ over I Ϫ (based on conductance measurements) and voltage-dependent gating, which is strongly dependent on the permeant ion concentration. In cases where the gating can be studied in detail, ClC channels have two gates: each subunit is gated by a permeant ion-and voltage-dependent mechanism (the so-called fast gate); in addition, both subunits are gated by a common (or slow) gate. ClC-1 is the principal skeletal muscle plasma chloride channel, and the classic disease associated with ClC channel dysfunction is Thomsen's disease (myotonia congenita), which results from mutations in the common gate of the mammalian ClC-1 such that the mutation has a strong dominant negative effect. But this is only one of many diseases associated with disrupted Cl Ϫ Figure 1. The ClC family of mammalian chloride channels. Based on sequence ho-mology, the nine mammalian ClC proteins can be grouped into three classes, of which the first (ClC-1,-ClC-2, ClC-Ka and ClC-Kb) is expressed primarily in plasma membranes , whereas the other two (ClC-3, ClC-4, and ClC-5 and ClC-6 and ClC-7) are expressed primarily in organ-ellar membranes. The primary functions, associated diseases, and phenotype of …