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Am J Physiol Renal Physiol 281: F206-F212, 2001;
0363-6127/01 $5.00
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Vol. 281, Issue 2, F206-F212, August 2001

Effect of dietary K intake on apical small-conductance K channel in CCD: role of protein tyrosine kinase

Yuan Wei, Peter Bloom, Daohong Lin, Ruimin Gu, and Wen Hui Wang

Department of Pharmacology, New York Medical College, Valhalla, New York 10595

We have used Western blot to examine the expression of cSrc protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP)-1D in the renal cortex, and the patch-clamp technique to determine the role of PTK in mediating the effect of dietary K intake on the small-conductance K (SK) channel in the cortical collecting duct (CCD). When rats were on a K-deficient (KD) diet for 1, 3, 5, and 7 days, the expression of cSrc increased by 40, 90, 140, and 135%, respectively. In contrast, the expression of cSrc in the renal cortex from rats on a high-K (HK) diet for 1, 2, and 3 days decreased by 40, 60, and 75%, respectively. However, the protein level of PTP-1D was not significantly changed by dietary K intake. The addition of 1 µM herbimycin A increased NPo, a product of channel number (N) and open probability (Po) in the CCD from rats on a normal diet or on a KD diet. The increase in NPo was 0.30 (normal), 0.45 (1-day KD), 0.65 (3-day KD), 1.55 (5-day KD), and 1.85 (7-day KD), respectively. Treatment of the CCD with herbimycin A from rats on a KD diet increased NPo per patch from the control value (0.7) to 1.4 (1-day KD), 1.6 (3-day KD), 2.6 (5-day KD), and 3.5 (7-day KD), respectively. In contrast, HK intake for as short as 1 day abolished the effect of herbimycin A. Furthermore, the expression of ROMK channels in the renal cortex was the same between rats on a KD diet or on a HK diet. Moreover, treatment with herbimycin A did not further increase NPo in the CCDs from rats on a HK diet. We conclude that dietary K intake plays a key role in regulating the activity of the SK channels and that PTK is involved in mediating the effect of the K intake on channel activity in the CCD.

hyperkalemia; hypokalemia; protein tyrosine phosphatase 1D; renal potassium secretion; cortical collecting duct


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