Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The protein kinase C (PKC) pathway is important for the regulation of K(+) transport. The renal outer medullar K(+) (ROMK1) channels show an exquisite sensitivity to intracellular protons (pH(i)) (effective pK(a) approximately 6.8) and play a key role in K(+) homeostasis during metabolic acidosis. Our molecular dynamic simulation results suggest that PKC-mediated phosphorylation on Thr-193 may disrupt the PIP(2)-channel interaction via a charge-charge interaction between Thr-193 and Arg-188. Therefore, we investigated the role of PKC and pH(i) in regulation of ROMK1 channel activity using a giant patch clamp with Xenopus oocytes expressing wild-type and mutant ROMK1 channels. ROMK1 channels pre-incubated with the PKC activator phorbol-12-myristate-13-acetate exhibited increased sensitivity to pH(i) (effective pK(a) shifted to pH approximately 7.0). In the presence of GF109203X--a PKC selective inhibitor--the effective pK(a) for inhibition of ROMK1 channels by pH(i) decreased (effective pK(a) shifted to pH approximately 6.5). The pH(i) sensitivity of ROMK1 channels mediated by PKC appeared to be dependent of PIP(2) depletion. The giant patch clamp together with site direct mutagenesis revealed that Thr-193 is the phosphorylation site on PKC that regulates the pH(i) sensitivity of ROMK1 channels. Mutation of PKC-induced phosphorylation sites (T193A) decreases the pH(i) sensitivity and increases the interaction of channel-PIP(2). Taken together, these results provide new insights into the molecular mechanisms underlying the pH(i) gating of ROMK1 channel regulation by PKC.
Cantone,
Mouse model of type II Bartter's syndrome. I. Upregulation of thiazide-sensitive Na-Cl cotransport activity.
2008, Pubmed
Cantone,
Mouse model of type II Bartter's syndrome. I. Upregulation of thiazide-sensitive Na-Cl cotransport activity.
2008,
Pubmed
Choe,
A conserved cytoplasmic region of ROMK modulates pH sensitivity, conductance, and gating.
1997,
Pubmed
,
Xenbase
DeCoy,
Anti sense DNA down-regulates proteins kinase C-epsilon and enhances vasopressin-stimulated Na+ absorption in rabbit cortical collecting duct.
1995,
Pubmed
Galkina,
Regulation of intracellular pH by cell-cell adhesive interactions.
1995,
Pubmed
Giebisch,
Renal tubule potassium channels: function, regulation and structure.
2000,
Pubmed
Hebert,
Molecular diversity and regulation of renal potassium channels.
2005,
Pubmed
Hilgemann,
Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2.
1996,
Pubmed
Ho,
Intracellular pH on translocation of protein kinase C isozymes in rat pinealocytes.
2000,
Pubmed
Ho,
Cloning and expression of an inwardly rectifying ATP-regulated potassium channel.
1993,
Pubmed
,
Xenbase
Huang,
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
1998,
Pubmed
,
Xenbase
Lee,
Functional and structural characterization of PKA-mediated pHi gating of ROMK1 channels.
2008,
Pubmed
,
Xenbase
Lee,
Gabapentin activates ROMK1 channels by a protein kinase A (PKA)-dependent mechanism.
2008,
Pubmed
,
Xenbase
Lee,
PKA-mediated phosphorylation is a novel mechanism for levetiracetam, an antiepileptic drug, activating ROMK1 channels.
2008,
Pubmed
,
Xenbase
Leng,
Subunit-subunit interactions are critical for proton sensitivity of ROMK: evidence in support of an intermolecular gating mechanism.
2006,
Pubmed
,
Xenbase
Leung,
Phosphatidylinositol 4,5-bisphosphate and intracellular pH regulate the ROMK1 potassium channel via separate but interrelated mechanisms.
2000,
Pubmed
,
Xenbase
Levitan,
Modulation of ion channels by protein phosphorylation and dephosphorylation.
1994,
Pubmed
Lin,
Protein kinase C (PKC)-induced phosphorylation of ROMK1 is essential for the surface expression of ROMK1 channels.
2002,
Pubmed
,
Xenbase
Liou,
Regulation of ROMK1 channel by protein kinase A via a phosphatidylinositol 4,5-bisphosphate-dependent mechanism.
1999,
Pubmed
,
Xenbase
Ma,
Acute regulation of epithelial sodium channel by anionic phospholipids.
2005,
Pubmed
Macica,
Role of the NH2 terminus of the cloned renal K+ channel, ROMK1, in arachidonic acid-mediated inhibition.
1998,
Pubmed
,
Xenbase
McNicholas,
pH-dependent modulation of the cloned renal K+ channel, ROMK.
1998,
Pubmed
,
Xenbase
Minami,
Effects of ethanol and anesthetics on type 1 and 5 metabotropic glutamate receptors expressed in Xenopus laevis oocytes.
1998,
Pubmed
,
Xenbase
Nasuhoglu,
Modulation of cardiac PIP2 by cardioactive hormones and other physiologically relevant interventions.
2002,
Pubmed
Proks,
Mutations within the P-loop of Kir6.2 modulate the intraburst kinetics of the ATP-sensitive potassium channel.
2001,
Pubmed
,
Xenbase
Rapedius,
H bonding at the helix-bundle crossing controls gating in Kir potassium channels.
2007,
Pubmed
,
Xenbase
Rapedius,
Structural and functional analysis of the putative pH sensor in the Kir1.1 (ROMK) potassium channel.
2006,
Pubmed
,
Xenbase
Sackin,
External K activation of Kir1.1 depends on the pH gate.
2007,
Pubmed
Sterling,
PKC expression is regulated by dietary K intake and mediates internalization of SK channels in the CCD.
2004,
Pubmed
Sugimoto,
Distinct cellular localization of mRNAs for three subtypes of prostaglandin E receptor in kidney.
1994,
Pubmed
Takeishi,
Transgenic overexpression of constitutively active protein kinase C epsilon causes concentric cardiac hypertrophy.
2000,
Pubmed
Tapper,
Protein kinase C and intracellular pH regulate zymosan-induced lysosomal enzyme secretion in macrophages.
1995,
Pubmed
Wang,
Dual modulation of renal ATP-sensitive K+ channel by protein kinases A and C.
1991,
Pubmed
Wang,
Regulation of ROMK (Kir1.1) channels: new mechanisms and aspects.
2006,
Pubmed
Wei,
Angiotensin II inhibits the ROMK-like small conductance K channel in renal cortical collecting duct during dietary potassium restriction.
2007,
Pubmed
Welling,
A comprehensive guide to the ROMK potassium channel: form and function in health and disease.
2009,
Pubmed
Wilborn,
Differential expression of PKC isoforms in fresh and cultured rabbit CCD.
1996,
Pubmed
Zeng,
Structural determinants and specificities for ROMK1-phosphoinositide interaction.
2002,
Pubmed
,
Xenbase
Zeng,
Protein kinase C inhibits ROMK1 channel activity via a phosphatidylinositol 4,5-bisphosphate-dependent mechanism.
2003,
Pubmed
,
Xenbase
Zhang,
Dual regulation of renal Kir7.1 potassium channels by protein Kinase A and protein Kinase C.
2008,
Pubmed
,
Xenbase
