NA-REGULATES AN ATP-SENSITIVE K+ CHANNEL IN RABBIT PROXIMAL CONVOLUTED TUBULE( PUMP INHIBITION DOWN)

In several epithelial and nonepithelial tissues a functional link betw een the basolateral Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase) and a basolateral K+ conductance has been established. However, the natur e of this link is unclear. We have previously identified a K+ channel on the basolateral membrane of the proximal convoluted tubule perfused in vitro, the activity of which is increased by stimulation of Na+ tr ansport [J. S. Beck, A. M. Hurst, J.-Y Lapointe. and R. Laprade. A m. J. Physiol. 264 (Renal Fluid Electrolyte Physiol. 33): F496-F501, 1993 .]. In the present study we investigate whether basolateral membrane K + channel activity is tightly coupled to Na+-K+-ATPase activity. In ce ll-attached patches (150 mM K+ pipette), following stimulation of chan nel activity by addition of Na+-cotransported solutes to the tubule lu men, mean channel open probability (NP(o)) was reduced from 0.35 +/- 0 .09 to 0.14 +/- 0.06 (n = 7, P < 0.05) by blocking the Na+-K+-ATPase w ith 100 muM strophanthidin. In excised patches the channel was reversi bly blocked by 2 mM ATP from the cytosolic face of the patch, such tha t NP(o) fell to 20.1 +/- 7.0% (n = 5, P < 0.001) of control and recove red to 52.2 +/- 11.2% (n = 5, P < 0.05) after washout of ATP. Diazoxid e, a putative opener of ATP-sensitive K+ channels, when added to the b athing solution of an unstimulated tubule (microperfused in the absenc e of Na+-cotransported solutes), increased NP(o) from 0.046 +/- 0.035 to 0.44 +/- 0.2 (n = 6, P < 0.05). These results demonstrate that the Na+-K+-ATPase is functionally coupled to a basolateral membrane K+ cha nnel through an intracellular messenger, possibly ATP.