Search Results - (Author, Cooperation:T. J. Jentsch)

2014-05-03

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Agammaglobulinemia/genetics ; *Cell Size ; Chloride Channels/*metabolism ; Gene Knockout Techniques ; Genome-Wide Association Study ; HCT116 Cells ; HEK293 Cells ; Humans ; Membrane Proteins/genetics/*metabolism ; Mutation ; Protein Multimerization ; RNA Interference ; RNA, Small Interfering/genetics ; Taurine/metabolism ; Transfection

1432-2013

Key words Anion channel ; Arabidopsis thaliana ; CBS domain ; Double-barrel ; Endocytosis ; Gating ; Human genetics ; Kidney stones ; Yeast gef1

Springer Online Journal Archives 1860-2000

Medicine

Abstract  Chloride channels perform important roles in the regulation of cellular excitability, in transepithelial transport, cell volume regulation, and acidification of intracellular organelles. This variety of functions requires a large number of different chloride channels that are encoded by genes belonging to several unrelated gene families. The CLC family of chloride channels has nine known members in mammals that show a differential tissue distribution and function both in plasma membranes and in intracellular organelles. CLC proteins have about 10–12 transmembrane domains. They probably function as dimers and may have two pores. The functional expression of channels altered by site-directed mutagenesis has led to important insights into their structure–function relationship. Their physiological relevance is obvious from three human inherited diseases (myotonia congenita, Dent’s disease and Bartter’s syndrome) that result from mutations in some of their members and from a knock-out mouse model.

Electronic Resource

1432-1424

Anion transport ; Chloride channel ; Cystic fibrosis ; Structure and function

Springer Online Journal Archives 1860-2000

Biology

Chemistry and Pharmacology

Conclusions Until recently, the study of chloride channels largely has been neglected. Interest in physiological processes such as stabilization of resting membrane potential, volume and pH regulation, and transepithelial transport has provided the impetus for acquiring our present understanding of chloride channels. Molecular biological techniques have proven useful in increasing our understanding of epithelial chloride channels, at the very least by providing a structural basis for functional data. Knowledge of the structure of several families of chloride channels has provided us with the capability to probe functional questions via structural manipulations, and yielded answers essential to gaming a more complete perspective of the role of chloride channels in epithelia. It may be anticipated that a large number of new chloride channels, and maybe even new chloride channel families, will be cloned in the next few years. A major challenge will be to elucidate their functions in the cell, the epithelium, and the organism as a whole.

Electronic Resource

1432-1424

corneal endothelium ; cell culture ; intracellular potential ; bicarbonate ; pH ; stilbenes

Springer Online Journal Archives 1860-2000

Biology

Chemistry and Pharmacology

Summary Micropuncture of cultured bovine corneal endothelial cells led to registrations stable for hours. Intracellular potentials were mainly in the range of −40 to −55 mV, average 46.3±0.6 mV (sem). Changes of extracellular [HCO 3 − ] led to voltage transients, their amplitude depending logarithmically on [HCO 3 − ] with a mean slope of 37.3±8.8 (sd) mV. After removal of bicarbonate/CO2, a steady-state depolarization was seen. This steady-state depolarization, but not the voltage transients, could be reduced by 1mm Ba++. After removal of bicarbonate, the voltage response to changes of extracellular potassium was reduced. Alteration of pH i induced by permeable buffers (butyrate, glycodiazine and ammonium) also resulted in voltage transients, internal acidification being correlated with a hyperpolarization, and internal alkalinization with a depolarization. Also changes of external pH caused voltage responses, alkalinization causing a hyperpolarization, acidification a depolarization. Methazolamide, an inhibitor of carbonic anhydrase, as well as stilbenes (SITS or DIDS) caused a reduction of the voltage response to HCO 3 − and pH. Their effects were additive. It is suggested that corneal endothelial cells possess one or two electrogenic transporters for HCO 3 − or related species, one of which is inhibitable by stilbenes.

Electronic Resource