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| MECHANISM OF APICAL K+ CHANNEL MODULATION IN PRINCIPAL RENAL TUBULE CELLS - EFFECT OF INHIBITION OF BASOLATERAL NA+-K+-ATPASE |
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| Author(s): WANG WH, GEIBEL J, GIEBISCH G |
| Source: JOURNAL OF GENERAL PHYSIOLOGY Volume: 101 Issue: 5 Pages: 673-694 Published: MAY 1993 |
| Times Cited: 58 References: 49 |
| Abstract: The effects of inhibition of the basolateral Na+-K+-ATPase (pump) on the apical low-conductance K+ channel of principal cells in rat cortical collecting duct (CCD) were studied with patch-clamp techniques. Inhibition of pump activity by removal of K+ from the bath solution or addition of strophanthidin reversibly reduced K+ channel activity in cell-attached patches to 36% of the control value. The effect of pump inhibition on K+ channel activity was dependent on the presence of extracellular Ca2+, since removal of Ca2+ in the bath solution abolished the inhibitory effect of 0 mM K+ bath. The intracellular [Ca2+] (measured with fura-2) was significantly increased, from 125 nM (control) to 335 nM (0 mM K+ bath) or 408 nM (0.2 mM strophanthidin), during inhibition of pump activity. In contrast, cell pH decreased only moderately, from 7.45 to 7.35. Raising intracellular Ca2+ by addition of 2 muM ionomycin mimicked the effect of pump inhibition on K+ channel activity. 0.1 mM amiloride also significantly reduced the inhibitory effect of the K+ removal. Because the apical low-conductance K channel in inside-out patches is not sensitive to Ca2+ (Wang, W., A. Schwab, and G. Giebisch. 1990. American Journal of Physiology. 259:F494-F502), it is suggested that the inhibitory effect of Ca2+ is mediated by a Ca2+-dependent signal transduction pathway. This view was supported in experiments in which application of 200 nM staurosporine, a potent inhibitor of Ca2+-dependent protein kinase C (PKC), markedly diminished the effect of the pump inhibition on channel activity. We conclude that a Ca2+-dependent protein kinase such as PKC plays a key role in the downregulation of apical low-conductance K+ channel activity during inhibition of the basolateral Na+-K+-ATPase. |
| Document Type: Article |
| Language: English |
| Reprint Address: WANG, WH (reprint author), YALE UNIV, SCH MED, DEPT CELLULAR & MOLEC PHYSIOL, 333 CEDAR ST, POB 3333, NEW HAVEN, CT 06510 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Physiology |
| IDS Number: LC793 |
| ISSN: 0022-1295 |
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