Electrodiffusional ATP movement through the cystic fibrosis transmembrane conductance regulator

Autor: Claudio Grosman, Dennis A. Ausiello, George R. Jackson, I. L. Reisin, Horacio F. Cantiello, Catherine R. O'Riordan, Steven C. Borkan, A. G. Prat, Yihan Wang
Rok vydání: 1998
Předmět:
Zdroj: American Journal of Physiology-Cell Physiology. 274:C799-C809
ISSN: 1522-1563
0363-6143
DOI: 10.1152/ajpcell.1998.274.3.c799
Popis: Expression of the cystic fibrosis transmembrane conductance regulator (CFTR), and of at least one other member of the ATP-binding cassette family of transport proteins, P-glycoprotein, is associated with the electrodiffusional movement of the nucleotide ATP. Evidence directly implicating CFTR expression with ATP channel activity, however, is still missing. Here it is reported that reconstitution into a lipid bilayer of highly purified CFTR of human epithelial origin enables the permeation of both Cl−and ATP. Similar to previously reported data for in vivo ATP currents of CFTR-expressing cells, the reconstituted channels displayed competition between Cl−and ATP and had multiple conductance states in the presence of Cl−and ATP. Purified CFTR-mediated ATP currents were activated by protein kinase A and ATP (1 mM) from the “intracellular” side of the molecule and were inhibited by diphenylamine-2-carboxylate, glibenclamide, and anti-CFTR antibodies. The absence of CFTR-mediated electrodiffusional ATP movement may thus be a relevant component of the pleiotropic cystic fibrosis phenotype.
Databáze: OpenAIRE