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

In several epithelial and nonepithelial tissues a functional link between the basolateral Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase) and a basolateral K+ conductance has been established. However, the nature 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+ transport [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 cell-attached patches (150 mM K+ pipette), following stimulation of channel activity by addition of Na+-cotransported solutes to the tubule lumen, 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 with 100 muM strophanthidin. In excised patches the channel was reversibly blocked by 2 mM ATP from the cytosolic face of the patch, such that NP(o) fell to 20.1 +/- 7.0% (n = 5, P < 0.001) of control and recovered to 52.2 +/- 11.2% (n = 5, P < 0.05) after washout of ATP. Diazoxide, a putative opener of ATP-sensitive K+ channels, when added to the bathing solution of an unstimulated tubule (microperfused in the absence 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+ channel through an intracellular messenger, possibly ATP.