Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2433K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lu, M. Articles by Giebisch, G. Search for Related Content PubMed PubMed Citation Articles by Lu, M. Articles by Giebisch, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Social Bookmarking                      What's this?

Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520

Address correspondence to Ming Lu, Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208026, New Haven, CT 06520. Fax: (203) 785-4951; E-mail: ming.lu{at}yale.edu

The small-conductance K⁺ channel (SK) in the apical membrane of the cortical-collecting duct (CCD) is regulated by adenosine triphosphate (ATP) and phosphorylation-dephosphorylation processes. When expressed in Xenopus oocytes, ROMK, a cloned K⁺ channel similar to the native SK channel, can be stimulated by phosphatidylinositol bisphosphate (PIP₂), which is produced by phosphoinositide kinases from phosphatidylinositol. However, the effects of PIP₂ on SK channel activity are not known. In the present study, we investigated the mechanism by which hydrolyzable ATP prevented run-down of SK channel activity in excised apical patches of principal cells from rat CCD. Channel run-down was significantly delayed by pretreatment with hydrolyzable Mg-ATP, but ATPS and AMP-PNP had no effect. Addition of alkaline phosphatase also resulted in loss of channel activity. After run-down, SK channel activity rapidly increased upon addition of PIP₂. Exposure of inside-out patches to phosphoinositide kinase inhibitors (LY294002, quercetin or wortmannin) decreased channel activity by 74% in the presence of Mg-ATP. PIP₂ added to excised patches reactivated SK channels in the presence of these phosphoinositide kinase inhibitors. The protein kinase A inhibitor, PKI, reduced channel activity by 36% in the presence of Mg-ATP. PIP₂ was also shown to modulate the inhibitory effects of extracellular and cytosolic ATP. We conclude that both ATP-dependent formation of PIP₂ through membrane-bound phosphoinositide kinases and phosphorylation of SK by PKA play important roles in modulating SK channel activity.

Key Words: cortical-collecting duct (CCD) • small-conductance potassium channel (SK) • adenosine triphosphate (ATP) • phosphoinositide kinase (PI kinase) • phosphatidylinositol bisphosphate (PIP₂)

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Nakamura, Y. Komagiri, T. Kojo, and M. Kubokawa Delayed and acute effects of interferon-{gamma} on activity of an inwardly rectifying K+ channel in cultured human proximal tubule cells Am J Physiol Renal Physiol, January 1, 2009; 296(1): F46 - F53. [Abstract] [Full Text] [PDF]

				S.-R. Jung, K. Kim, B. Hille, T. D. Nguyen, and D.-S. Koh Pattern of Ca2+ increase determines the type of secretory mechanism activated in dog pancreatic duct epithelial cells J. Physiol., October 1, 2006; 576(1): 163 - 178. [Abstract] [Full Text] [PDF]

				S. C. Hebert, G. Desir, G. Giebisch, and W. Wang Molecular Diversity and Regulation of Renal Potassium Channels Physiol Rev, January 1, 2005; 85(1): 319 - 371. [Abstract] [Full Text] [PDF]

				D. Enkvetchakul and C.G. Nichols Gating Mechanism of KATP Channels: Function Fits Form J. Gen. Physiol., October 27, 2003; 122(5): 471 - 480. [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents