Cystic fibrosis transmembrane conductance regulator facilitates ATP release by stimulating a separate ATP release channel for autocrine control of cell volume regulation

These studies provide evidence that cystic fibrosis transmembrane conductan ce regulator (CFTR) potentiates and accelerates regulatory volume decrease (RVD) following hypotonic challenge by an autocrine mechanism involving ATP release and signaling. In wild-type CFTR-expressing cells, CFTR augments c onstitutive ATP release and enhances ATP release stimulated by hypotonic ch allenge. CFTR itself does not appear to conduct ATP. Instead, ATP is releas ed by a separate channel, whose activity is potentiated by CFTR. Blockade o f ATP release by ion channel blocking drugs, gadolinium chloride (Gd3+) and 4,4'-diisothiocyanatostilbene-2,2'disulfonic acid (DIDS), attenuated the e ffects of CFTR on acceleration and potentiation of RVD. These results suppo rt a key role for extracellular ATP and autocrine and paracrine purinergic signaling in the regulation of membrane ion permeability and suggest that C FTR potentiates ATP release by stimulating a separate ATP channel to streng then autocrine control of cell volume regulation.