Na+ pump inhibition downregulates 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. Am. 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 (NPo) 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 microM strophanthidin. In excised patches the channel was reversibly blocked by 2 mM ATP from the cytosolic face of the patch, such that NPo 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 NPo from 0.046 +/- 0.035 to 0.44 +/- 0.2 (n = 6, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Groupe de Recherche en Transport Membranaire, Université de Montréal, Quebec, Canada.
A M
AM
Hurst
J S
JS
Beck
R
R
Laprade
J Y
JY
Lapointe
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D015536:Down-Regulation / Q000502:physiology*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D013327:Strophanthidin / Q000494:pharmacology
D015221:Potassium Channels; D013327:Strophanthidin; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D003981:Diazoxide