CFTR is a chloride channel whose gating process involves coordinated interactions among the regulatory (R) domain and the nucleotide-binding folds (NBFs). Protein kinase A phosphorylation of serine residues renders the R domain from inhibitory to stimulatory and enables ATP binding and hydrolysis at the NBFs, which in turn control opening and closing of the chloride channel.

The gating component associated with the voltage-sensitive Na+ channel from electroplax membranes of Electrophorus electricus has been purified by using toxin gamma from the venom of the scorpion Tityus serrulatus serrulatus. The toxin-binding site was efficiently solubilized with Lubrol PX, resulting in an extract of high initial specific activity. Purification was achieved by adsorption of th...

a variety of other vasoactive agents, calcium ionophore, phorbol ester, or cyclic GMP. The cyclic AMP-induced configurational change was completely inhibited by 2.5 mM N-phenylanthranilic acid or 145 mM sodium gluconate (Clchannel inhibitors) and was partially inhibited by 2.5 mM 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), but it was not affected by deprivation of Ca2' or...

Ivermectin is an oral semi-synthetic lactone anthelmintic agent derived from avermectins isolated from fermentation products of Streptomyces avermitilis. Ivermectin showed a concentration-dependent inhibitory effect on motility of a free-living nematode, Caenorhabditis elegans (C. elegans). There exist specific binding sites having a high affinity for ivermectin in the membrane fraction of C. e...

Objective: In a previous work, we showed that asafoetida essential oil (AEO), from oleo-gum resin of Ferula asafoetida L. from the Apiaceae family, has a vasodilatory effect. This effect was both endothelium-dependent and endothelium-independent. The present study was designed to determine whether potassium channels and intracellular calcium release contribute to AEO-i...

A distinctive feature of the voltage-dependent chloride channels ClC-0 (the Torpedo electroplaque chloride channel) and ClC-1 (the major skeletal muscle chloride channel) is that chloride acts as a ligand to its own channel, regulating channel opening and so controlling the permeation of its own species. We have now studied the permeation of a number of foreign anions through ClC-1 using voltag...

Caenorhabditis elegans spermatogenesis is especially suited for studies of nonrandom cytoplasmic segregation during cellular differentiation. Spermatocytes separate from an anuclear cytoplasmic core and undergo two sequential divisions. During the second division, intracellular organelles segregate specifically to spermatids as they bud from an anuclear residual body. We have applied patch-clam...

Ivermectin is a widely used anthelmintic drug whose nematocidal mechanism is incompletely understood. We have used Caenorhabditis elegans as a model system to understand ivermectin's effects. We found that the M3 neurons of the C.elegans pharynx form fast inhibitory glutamatergic neuromuscular synapses. avr-15, a gene that confers ivermectin sensitivity on worms, is necessary postsynaptically f...

The activity of calcium-activated chloride channels is controlled through the complex interaction of cellular mechanisms affecting calcium entry, buffering, and extrusion, and an unknown stoichiometric relation between intracellular Ca concentration and Cl channel activation. Here, we show that calcium-activated chloride current [ICl(Ca)] in cone photoreceptors is also highly sensitive to exter...

Two major discoveries have transformed our understanding of cystic fibrosis, a genetic disease in which thick secretions accumulate in airways, digestive organs and sperm duct. The first was that cystic fibrosis involves a basic defect in epithelial ion transport [1], which is manifested primarily as the loss of chloride conductance [2]. The connection between the loss of epithelial chloride co...