gramicidin-a and cetiedil

Cetiedil, a drug that is reported to block K+-channels, substantially increases the conductive C1- permeability of Chinese hamster ovary (CHO) cells. The permeability was monitored by volume changes in cells treated with gramicidin to increase the cation permeability. Under this circumstance, increases in Cl- conductances result in volume changes detectable by electronic sizing, with the direction determined by the gradients of the permeating ions. In NaCl or KCl media, swelling occurs, but in N-methylglucamine chloride, shrinking. The increases in Cl- conductance could also be measured as an increased 36Cl- flux or by changes in membrane potential (measured by fluorescence of a potential-sensitive dye) toward the Cl- equilibrium potential. The effect of cetiedil was concentration dependent, with maximal effect at 50 microM. The anion specificity for the conductance was NO3- greater than Cl- = Br- much greater than SO4-2 or isethionate. A number of other drugs that influence transport activities had no effect on Cl- conductance. The cetiedil effect on Cl- conductance was observed in one other cell line, but was absent in several other cell types. The cetiedil-induced Cl- conductance in CHO cells appears to involve a different pathway than that induced by exposure to hypotonic medium.

Topics: Animals; Anions; Azepines; Cell Line; Cell Membrane Permeability; Chlorides; Cricetinae; Cricetulus; Female; Fibroblasts; Gramicidin; Membrane Potentials; Ovary; Potassium; Sodium

Human peripheral blood lymphocytes (PBL), when placed into hypotonic media, first swell and then shrink back to their original volumes because of a rapid KCl leakage via volume-activated K+ and anion permeation pathways. By using gramicidin, a cation channel-forming ionophore, cation transport through the cell membrane can be shunted so that the salt fluxes and thus the volume changes are limited by the rate of the net anion movements. The "gramicidin method," supplemented with direct measurements of volume-induced ion fluxes, can be used to assess the effects of drugs and of various treatments on cation and anion permeabilities. It is demonstrated that quinine and cetiedil are much more effective blockers of volume-induced K+ transport than of Cl- transport, while dipyridamole, DIDS, and NIP-taurine inhibit only volume-induced Cl- movement. Oligomycins block both cation and anion transport pathways, oligomycin A being more effective in inhibiting K+ transport and oligomycin C preferentially blocking Cl- movement. Ca depletion of PBL abolishes volume-induced K+ transport but has no effect on Cl- transport. Repletion of cell calcium by ionophore A23187 immediately restores rapid K+ transport without significantly affecting volume-induced Cl- transport. These observations, taken together with other reported information, can be best explained by a model in which cell swelling activates independent Cl- and K+ conductance pathways, the latter being similar in properties to the Ca2+-activated K+ transport observed in various cell membranes.

Topics: Azepines; Capillaries; Cell Membrane Permeability; Chlorides; Electric Conductivity; Gramicidin; Humans; Hypotonic Solutions; Lymphocytes; Oligomycins; Potassium