cAMP stimulation of CFTR-expressing Xenopus oocytes activates a chromanol-inhibitable K+ conductance

Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a Cl- channel in a large variety of cells expressing this protein. Recently evidence has accumulated that it also regulates other ion channels. A coordinated increase in Cl- and K+ conductances is necessary in many Cl--secreting epithelia. This has, for example, recently been demonstrated for the colonic crypt, for which a new type of K+ channel and a specific inhibitor of this channel, the chromanol 293B, have been described. In the present study we have examined whether the cAMP-evoked activation of CFTR, overexpressed in Xenopus oocytes, in addition to its known activation or a Cl- conductance, also upregulates endogenous K+ channels. It is shown that CFTR-cRNA-injected but nor: water-injected oocytes possess a cAMP-activated Cl- conductance, Of the cAMP-induced whole-cell cut-rent increase, 15-25% was due to a 293B-, Ba2+ and TEA(+)-inhibitable K+ conductance. The cRNA of the mutated CFTR (Delta F508 CFTR) had no such effect, We conclude that cAMP activated CFTR and ail endogenous IsK-type and 293B-sensitive K+ conductance. Similar events, occurring, for example, in the colonic crypt possessing CFTR an d293B-sensitive K+ channels, might explain the coordinated cAMP-mediated increase in Cl- and K+ conductances.