RESUMO
A C2 symmetric small molecule composed of l-phenylalanine and isophthalamide was found to function as a Cl(-)/HCO3(-) dual transporter and self-assemble into chloride channels. In Ussing-chamber based short-circuit current measurements, this molecule elicited chloride-dependent short-circuit current (Isc) increase in both Calu-3 cell and CFBE41o-cell (with F508del mutant CFTR) monolayers.
Assuntos
Bicarbonatos/metabolismo , Canais de Cloreto/química , Cloretos/metabolismo , Transporte Biológico , Células Cultivadas , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Humanos , Espectroscopia de Ressonância Magnética , MutaçãoRESUMO
In living cell membranes, K(+) permeability is higher than that of other ions such as Na(+) and Cl(-) owing to abundantly expressed K(+) channels. Polarized membrane potential is mainly established by K(+) outward flow because the K(+) concentration in the intracellular side is much higher than that in the extracellular side. We have found that the small synthetic molecule 1 is capable of self-assembling into selective K(+) channels, enhancing K(+) permeability and hyperpolarizing liposome membrane potential. Interestingly, molecule 1 also functions as K(+) channel hyperpolarizing living cell membrane potential and relaxing agonist-induced blood vessel contraction. Therefore, it may have the potential to become a lead compound for the treatment of human diseases associated with K(+) channel dysfunction.
