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Mechanoregulation of BK channel activity in the mammalian cortical collecting duct: role of protein kinases A and C.
- Source :
-
American Journal of Physiology: Renal Physiology . Oct2009, Vol. 297, pF904-F915. 12p. - Publication Year :
- 2009
-
Abstract
- Flow-stimulated net K secretion (Jκ) in the cortical collecting duct (CCD) is mediated by an iberiotoxin (IBX)-sensitive BK channel, and requires an increase in intracellular Ca2+ concentration ([Ca2+],). The a-subunit of the reconstituted BK channel is phosphorylated by PKA and PKC. To test whether the BK channel in the native CCD is regulated by these kinases, Jκ and net Na absorption (JNa) were measured at slow (∼1) and fast (∼5 nl·min-1· mm-1) flow rates in rabbit CCDs microperfused in the presence of mPKI, an inhibitor of PKA; calphostin C, which inhibits diacyiglycerol binding proteins, including PKC; or bisindolylmaleimide (BIM) and Gö6976, inhibitors of classic and novel PKC isoforms, added to luminal (L) and/or basolateral (B) solutions. L but not B mPKI increased Jκ in CCDs perfused at a slow flow rate; a subsequent increase in flow rate augmented Jκ modestly. B mPKI alone or with L inhibitor abolished flow stimulation of Jκ. Similarly, L calphostin C increased Jκ in CCDs perfused at slow flow rates, as did calphostin C in both L and B solutions. The observation that IBX inhibited the L mPKI and calphostin C-mediated increases in Jκ at slow flow rates implicated the BK channel in this K flux, a notion suggested by patch-clamp analysis of principal cells. The kinase inhibited by calphostin C was not PKC as L and/or B BIM and Gö6976 failed to enhance Jκ at the slow flow rate. However, addition of these PKC inhibitors to the B solution alone or with L inhibitor blocked flow stimulation of Jκ. Interpretation of these results in light of the effects of these inhibitors on the flow-induced elevation of [Ca2+]i suggests that the principal cell apical BK channel is tonically inhibited by PKA and that flow stimulation of Jκ in the CCD is PKA and PKC dependent. The specific targets of the kinases remain to be identified. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1931857X
- Volume :
- 297
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Renal Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 44657488
- Full Text :
- https://doi.org/10.1152/ajprenal.90685.2008