Chloride currents

C1C-6 and C1C-7 define the third branch of the CLC family. These proteins are only about 45% identical to each other. Whereas CLC-7 is very broadly expressed, the CLC-6 protein seems to be restricted to the nervous system. It proved impossible to obtain plasma membrane chloride currents with either C1C-6 or C1C-7. This is due to the fact that both channels reside in intracellular organelles under most circumstances. Based on structural features, it appeals likely that they also mediate CF/H + exchange. 

The newest molecular addition to Cl- channels are bestrophins [5]. There are four different bestrophin isoforms in humans. Mutations in Bestl cause Best macular dystrophy, hence their name. All four isoforms induce chloride currents when expressed heterologously. Although they show a dependence on intracellular calcium, their biophysical properties differ from Ca-activated chloride currents typically observed in native cells. Mutagenesis experiments changed the activation of currents and induced slight changes in ion selectivity, lending support to the hypothesis that bestrophins themselves are Cl- channels. 

GABAa receptors are pentameric complexes on the postsynaptic membrane with a central pore with selectivity for chloride ions. Benzodiazepines and barbiturates increase the GABA-induced chloride currents, leading to hyperpolarization of the postsynaptic membrane. 

The corrector activity of 15 was not limited to recombinant systems as it was confirmed in cultured HBE cells isolated from F508del homozygous patients. After 48-h incubation with 6.7 pM 15, a 2-fold increase in forskolin-stimulated chloride current (compared to DMSO-treated cells) or 14% of the response obtained in non-CF-HBE was observed. It was also reported that 14 and 15 increase the cell surface density of other trafficking-deficient proteins, including G601S-hERG. The authors speculate that this class of compounds may act on the folding pathway shared by both misfolded proteins rather than on CFTR itself [16]. 

Kurahashi, T. and Yau, K. W. Olfactory transduction. Tale of an unusual chloride current. Curr. Biol. 4 256-258,1994. 

Valverde MA, Mintenig GM, Sepulveda FV (1993) Differential effects of tamoxifen and I- on three distinguishable chloride currents activated in T84 intestinal cells. Pfliigers Arch 425(5-6) 552-554... 

Wagner, J. A., T. V. McDonald, P. T. Nghiem, A. W. Lowe, H. Schulman, D. C. Gruenert, L. Stryer, and P. Gardner. 1992. Antisense oligodeoxynucleotides to the cystic fibrosis transmembrane conductance regulator inhibit cAMP-activated but not calcium-activated chloride currents. Proc Natl Acad Sci USA 89(15) 6785-9. 

Miledi R, Parker 1. 1984. Chloride current induced by injection of calcium into Xenopus oocytes. J Physiol 357 173. 

Kokate TG, Svensson BE, Rogawski MA Anticonvulsant activity of neurosteroids correlation with g-aminobutyric acid-evoked chloride current potentiation. J Pharmacol Exp Ther 270 1223-1229, 1994... 

Bulteau-Pignoux L, Derand R, Metaye T, Joffre M, Becq F. 2002. Genistein modifies the activation kinetics and magnitude of phosphorylated wild-type and G551D-CFTR chloride currents. J Membr Biol 188 175-182. 

Chen, L., Wang, L., Zhu, L., Nie, S., Zhang, J., Zhong, P., Cai, B., Luo, H. and Jacob, T. J., 2002, Cell cycle-dependent expression of volume-activated chloride currents in nasopharyngeal carcinoma cells. 

Apart from HCN channels, genistein (42) also acted on other types of channels present in cardiac cells. Chiang et al. [306] examined the impact of this isoflavone on the L-type calcium and cAMP- dependent chloride currents in guinea pig ventricular myocytes. Using the voltage-clamp technique they found that genistein (42) reversibly inhibited L-type calcium currents in a dose-dependent manner. Surprisingly daidzein (40), which was ineffective with respect to many other channel types, also decreased L-type calcium currents in myocytes. Opposite to calcium currents, the cAMP-dependent... 

JP Arena, KK Liu, PS Paress, EG Frazier, DF Cully, H Mrozik, JM Schaeffer. The mechanism of action of avermectins in Caenorhabditis elegans correlation between activation of glutamate-sensitive chloride current, membrane binding, and biological activity. J Parasitol 81 286-294, 1995. 

The 5-HT4 receptors modulate the activities of channels and transporters by increasing cAMP levels. These include activation of L-type Ca2+ channels (326), chloride currents in human jejunal mucosa and rat distal colon (330,331), and the If pacemaker current in atrial myocytes (332) and stimulation of aldosterone release from the adrenal glands (333,334), striatal dopamine release (324), hippocampal and frontal cortex acetylcholine release (335,336), and hippocampal 5-HT release (337). 5-HT4 receptors also inhibit various channels, including a KV3.2-like delayed rectifier K+ channel (303), a voltage-activated K+ channel in colliculi neurons (320,338), a Ca2+-activated, afterhyperpolariz-ing, and K+ current in hippocampus (325). 

The amount of energy consumed depends upon the voltage across the bath and the current efficiency of the electrolyticaJ process. Although three products alkali hydroxide, chlorine, and hydrogen are obtained when electrolyzing a solution of sodium or potassium chloride, current efficiency is usually assessed by the resultant caustic which is the main product. 

A 10% brine solution contains about 6,000-ppm chloride. Current Environmental Protection Agency (EPA) guidelines call for a chronic (or continuous) chlorine discharge limit of 230 ppm to a controlled watercourse. 

Tanaka H, Shigenobu K (2000) AHC-52, a dihydropyridine compound with chloride current-blocking and cardioprotective activities. Cardiovasc Drug Rev 18 93-102... 

Horminone Salvia deserta, Plectranthus GABAA-R chloride current... 

Waglerin-1 (= 22 amino acid peptide)] (polypeptide) Wagler s pit viper venom GABAA-R chloride current block (3)... 

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