ELECTROPHYSIOLOGICAL EFFECTS OF EXTRACELLULAR ATP ON NECTURUS GALLBLADDER EPITHELIUM

The effects of addition of ATP to the mucosal bathing solution on transepithelial, apical, and basolateral membrane voltages and resistances in Necturus gallbladder epithelium were determined. Mucosal ATP (100-mu-M) caused a rapid hyperpolarization of both apical (V(mc)) and basolateral (V(cs)) cell membrane voltages (DELTA-V(m) = 18 +/- 1 mV), a fall in transepithelial resistance (R(t)) from 142 +/- 8 to 122 +/- 7 OMEGA.cm2, and a decrease in fractional apical membrane resistance (fR(a)) from 0.93 +/- 0.02 to 0.83 +/- 0.03. The rapid initial hyperpolarization of V(mc) and V(cs) was followed by a slower depolarization of cell membrane voltages and a lumen-negative change in transepithelial voltage (V(ms)). This phase also included an additional decrease in fR(a). Removal of the ATP caused a further depolarization of membrane voltages followed by a hyperpolarization and then a return to control values. fR(a) fell to a minimum after removal of ATP and then returned to control values as the cell membrane voltages repolarized. Similar responses could be elicited by ADP but not by adenosine. The results of two-point cable experiments revealed that ATP induced an initial increase in cell membrane conductance followed by a decrease. Transient elevations of mucosal solution [K+] induced a larger depolarization of V(mc) and V(cs) during exposure to ATP than under control conditions. Reduction of mucosal solution [Cl-] induced a slow hyperpolarization of V(mc) and V(cs) before exposure to ATP and a rapid depolarization during exposure to ATP. We conclude that ATP4- is the active agent and that it causes a concentration-dependent increase in apical and basolateral membrane K+ permeability. In addition, an apical membrane electrodiffusive Cl- permeability is activated by ATP4-.