ATP is a Coupling Modulator of Parallel Na,K-ATPase-K-Channel Activity in the Renal Proximal Tubule

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 14; pp. 6418 - 6422
• Main Authors: Tsuchiya, K., Wang, W., Giebisch, G., Welling, P. A.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.07.1992; National Acad Sciences; National Academy of Sciences
• Subjects: Adenosine triphosphatases; Adenosine Triphosphate - physiology; Animals; ATP; Biochemistry; Biological and medical sciences; Cell membranes; Cell physiology; Fundamental and applied biological sciences. Psychology; Glyburide - pharmacology; In Vitro Techniques; Ion Channel Gating; Kidney Tubules, Proximal - physiology; Kidneys; Membrane and intracellular transports; Membrane potential; Membrane Potentials - drug effects; Modulated signal processing; Molecular and cellular biology; Na super(+)/K super(T)-transporting ATPase; P branes; Physiological transport; Physiology; Potassium - metabolism; Potassium Channels - physiology; Proximal tubules; Pumps; Rabbits; Recycling; role; Signal Transduction; Sodium - metabolism; Sodium-Potassium-Exchanging ATPase - physiology; Enzyme; Electrophysiology; Rabbit; Ion transport; Ionic channel; Lagomorpha; Kidney; Vertebrata; Regulation(control); Mammalia; Na,K-ATPase; Coupling; Intracellular; ATP; Potassium; Proximal tube
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.14.6418

A fundamental and essential property of nearly all salt-transporting epithelia is the tight parallel coupling between the magnitude of the K-conductive pathway at the basolateral membrane and the activity of the Na,K-dependent ATPase (Na,K-ATPase). In the present study, we demonstrate that the coupling response in the renal proximal tubule is governed, at least in part, through the interaction between ATP-sensitive K channels and Na,K-ATPase-mediated changes in intracellular ATP levels. First, we identified a K-selective channel at the basolateral membrane, which is inhibited by the cytosolic addition of ATP. Second, conventional microelectrode analysis in the isolated perfused proximal straight tubule revealed that these channels are the major determinant of the macroscopic K conductance so that ATP-mediated changes in the open probability of the K channel could alter the extent of K recycling. Indeed, the increase in the macroscopic K conductance upon stimulation of transcellular Na transport and pump activity was found to be paralleled by a decrease in intracellular ATP. Finally, a causal link between parallel Na,K-ATPase-K-channel activity and ATP was established by the finding that intracellular ATP loading uncoupled the response. With our recent observations that similar ATP-sensitive K channels are expressed abundantly in other epithelia, we postulate that ATP may act as a universal coupling modulator of parallel Na,K-ATPase-K-channel activity.