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Am J Physiol Renal Physiol 286: F1072-F1078, 2004; doi:10.1152/ajprenal.00425.2003
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PKC expression is regulated by dietary K intake and mediates internalization of SK channels in the CCD

Hyacinth Sterling,1 Dao-Hong Lin,1,2 Yu-Jung Chen,1 Yuan Wei,1 Zhi-Jian Wang,1 Jian Lai,1 and Wen-Hui Wang1

1Department of Pharmacology, New York Medical College, Valhalla, New York 10595; and 2Department of Pharmacology, Harbin Medical University, Harbin 150086, China

Submitted 3 October 2003 ; accepted in final form 21 January 2004

We have used Western blot analysis and immunocytochemistry to determine the effect of dietary K intake on the expression of protein kinase C (PKC) isoforms in the kidney. Western blot has demonstrated that conventional PKC isoforms ({alpha} and {beta}), novel PKC isoforms ({delta}, {epsilon}, and {eta}), and atypical PKC isoforms ({zeta}) are expressed in the renal cortex and outer medulla. Moreover, a low K intake significantly increases the expression of PKC-{epsilon} in the renal cortex and outer medulla but does not change the expression of PKC-{alpha}, PKC-{beta}, PKC-{delta}, PKC-{eta}, and PKC-{zeta}. Also, immunocytochemistry shows that PKC-{epsilon} isoform is expressed in the cortical collecting duct (CCD) and outer medullary collecting duct (OMCD) and that the intensity of PKC-{epsilon} staining is higher in the kidney from rats on a K-deficient diet than those on a control diet. Also, we used the patch-clamp technique to study the role of PKC in mediating internalization of ROMK (Kir 1.1)-like small-conductance K (SK) channels induced by phenylarsine oxide (PAO), an agent that inhibits protein tyrosine phosphatase and has been shown to stimulate the internalization of the SK channel in the CCD (Sterling H, Lin DH, Qu RM, Dong K, Herbert SC, and Wang WH. J Biol Chem 277: 4317–4323, 2002). Inhibition of PKC with calphostin C and GF-109203x had no significant effect on channel activity but abolished the inhibitory effect of PAO on SK channels. In conclusion, a low K intake increases the expression of PKC-{epsilon} isoform in the renal cortex and outer medulla, and PKC is involved in mediating the internalization of SK channels in the CCD induced by stimulation of protein tyrosine kinase activity.

protein tyrosine kinase; ROMK (Kir 1.1); endocytosis; hypokalemia; potassium secretion



Address for reprint requests and other correspondence: W.-H. Wang, Dept. of Pharmacology, BSB Rm. 537, New York Medical College, Valhalla, NY 10595 (E-mail: wenhui_wang{at}nymc.edu).




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