PROPERTIES OF AN INWARDLY RECTIFYING ATP-SENSITIVE K+ CHANNEL IN THE BASOLATERAL MEMBRANE OF RENAL PROXIMAL TUBULE

The potassium conductance of the basolateral membrane (BLM) of proxima l tubule cells is a critical regulator of transport since it is the ma jor determinant of the negative cell membrane potential and is necessa ry for pump-leak coupling to the Na+,K+-ATPase pump. Despite this pivo tal physiological role, the properties of this conductance have been i ncompletely characterized, in part due to difficulty gaining access to the BLM. We have investigated the properties of this BLM K+ conductan ce in dissociated, polarized Ambystoma proximal tubule cells. Nearly a ll seals made on Ambystoma cells contained inward rectifier K+ channel s (gamma(slope,in) = 24.5 +/- 0.6 pS, gamma(chord,out) = 3.7 +/- 0.4 p S). The rectification is mediated in part by internal Mg2+. The open p robability of the channel increases modestly with hyperpolarization. T he inward conducting properties are described by a saturating binding- unbinding model. The channel conducts Tl+ and K+, but there is no sign ificant conductance for Na+, Rb+, Cs+, Li+, NH4+, or Cl-. The channel is inhibited by barium and the sulfonylurea agent glibenclamide, but n ot by tetraethylammonium. Channel rundown typically occurs in the abse nce of ATP, but cytosolic addition of 0.2 mM ATP (or any hydrolyzable nucleoside triphosphate) sustains channel activity indefinitely. Phosp horylation processes alone fail to sustain channel activity. Higher do ses of ATP (or other nucleoside triphosphates) reversibly inhibit the channel. The K+ channel opener diazoxide opens the channel in the pres ence of 0.2 mM ATP, but does not alleviate the inhibition of millimola r doses of ATP. We conclude that this K+ channel is the major ATP-sens itive basolateral K+ conductance in the proximal tubule.