The physiology of anion transport: tales of the bizarre and unexpected

This issue contains a series of papers generated by the speakers at a recent focused meeting entitled Physiology of Anion transport which was held at the University of Bristol on the 23–24th of July 2005. Students of anion transport are regularly challenged with weirdness: Cl− channels that behave as double-barrelled shotguns (Miller, 1982), an ABC transporter that behaves as an anion channel (Bear et al. 1992) and a Cl− channel that functions as a Cl−–H+ exchanger (Accardi & Miller, 2004) to give but three examples. The latest celebration of the bizarre and unexpected in the field of anion transport was the Physiology of Anion Transport meeting that was held at the University of Bristol, 23–24th July 2005. The meeting was a satellite conference of the Joint International Meeting of The Physiological Society and FEPS, and the fourth in a series of lively biannual International Anion Transport meetings. The Physiological Society and Active Pass, the Canadian Cystic Fibrosis Foundation, CED, the Cystic Fibrosis Foundation (USA), Digitimer Ltd, GRI, Leica Microsystems (UK) Ltd, Nature, Newport Ltd, NIH, Nikon UK Ltd, Novartis, Sanofi-Aventis, Scientifica Ltd, The Great Britain Sasakawa Foundation and Vertex Pharmaceuticals Inc. generously supported the Physiology of Anion Transport meeting. This issue of Experimental Physiology contains a collection of papers highlighting the major themes of the Physiology of Anion Transport meeting. The cystic fibrosis transmembrane conductance regulator (CFTR), unique among all known ion channels, was the focus of a number of talks at the meeting. A flavour of the presentations is provided by the papers of Paul Linsdell (Dalhousie, Canada) and Anil Mehta (Dundee, UK). Paul Linsdell discusses the molecular mechanisms of chloride permeation in the CFTR Cl− channel, which have been gleaned from functional studies of wild-type CFTR and variants containing site-directed mutations. His report provides an up-to-date summary of the important domains and amino acid residues that regulate the anion conduction and permeation of CFTR (Linsdell, 2005). In contrast, Anil Mehta discusses the novel concept that disruption of cell volume regulation might underlie the pathogenesis of cystic fibrosis. His paper (Treharne et al. 2005) highlights how the intracellular chloride concentration of epithelial cells modulates the phosphorylation status of transport proteins (e.g. CFTR) and hence their activity. Anion transport meetings are not complete without the identification and cloning of at least one putative new transport protein. The Physiology of Anion Transport meeting proved no exception. However, Makoto Suzuki (Tochigi, Japan) demonstrates convincingly that the protein encoded by the Drosophila mutant gene, tweety, and its two human homologues (hTTYH1 and hTTYH3) are none other than the large-conductance Cl− channels whose countless subconductance states and peculiar gating behaviour have tortured many students of anion channels (Suzuki, 2005). Of note, hTTYH3 is regulated by the intracellular Ca2+ concentration, whereas hTTYH1 is gated by cell swelling, so we can anticipate further weirdness when the mechanisms of gating of hTTYH1 and hTTYH3 are elucidated. Michel Pusch (Genova, Italy) discusses the very exciting and topical finding that two members of the CLC family of proteins (ClC-4 and ClC-5) function as Cl−–H+ antiporters and not Cl− channels as originally anticipated (Pusch et al. 2005). Building on the revelation of Accardi & Miller (2004) that ClC-ec1, a bacterial CLC protein, is a Cl−–H+ antiporter, Michel Pusch's data, together with those of Accardi & Miller (2004) and Scheel et al. (2005), have very important implications for the physiological role of CLC proteins in intracellular organelles. Together with the atomic resolution structural information available for ClC-ec1 (Dutzler et al. 2002), these unexpected discoveries will surely open up new avenues of research into how proteins with ion channel characteristics function as antiporters. Finally, Seth Alper (Harvard, USA) focuses on the molecular physiology and pathophysiology of the SLC4/AE family of anion exchangers (Alper, 2005). The 10 SLCA4 members are involved in diverse activities, including regulating intracellular pH, chloride activity and cell volume. Malfunction of these proteins causes a number of genetic diseases, including certain forms of anaemia and distal renal tubular acidosis (SLC4A1). Seth Alper's report summarizes detailed structure–function analyses of SLC4 proteins, which have identified specific protein regions important for determining anion selectivity, regulation by intra- and extracellular pH and sensitivity to intracellular calcium. Overall, the new data that have emerged provide a lucid understanding of how these transporters operate at the molecular level. Collectively, these five reports reflect some of the major advances in our understanding of the physiology of anion transporters and provide an excellent summary of recent progress in the field. We strongly encourage you to delve into these papers and explore the weirdness and wonder of anion transport!

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.