HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/C1145    most recent 00627.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Wang, Y. Articles by Huang, P. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Huang, P.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Regulation of CFTR channels by HCO₃^–-sensitive soluble adenylyl cyclase in human airway epithelial cells

Department of Biology, Hong Kong University of Science and Technology, Kowloon, Hong Kong, People's Republic of China

Submitted 21 December 2004 ; accepted in final form 14 June 2005

CFTR channels conduct HCO₃^– in addition to Cl^– in airway epithelial cells. A defective HCO₃^–-transporting function of CFTR may underlie the pathogenesis of cystic fibrosis. In the present study, we have investigated whether a HCO₃^–-sensitive soluble adenylyl cyclase (sAC) is functionally coupled with CFTR and thus forms an autoregulatory mechanism for HCO₃^– transport in human airway epithelial Calu-3 cells. A reverse transcriptase-polymerase chain reaction showed that transcripts of both full-length and truncated sACs are present in Calu-3 cells. Truncated sAC protein is the predominant, if not the only, isoform expressed in Calu-3 cells. HCO₃^– stimulated a modest increase in cAMP production, and the increase was sensitive to 2-hydroxyestradiol (2-HE), a sAC inhibitor, but not to SQ22,536, a blocker of conventional transmembrane adenylyl cyclases. These results suggest that sAC is functional in Calu-3 cells. Adding 25 mM HCO₃^– to the bath stimulated CFTR-mediated whole cell currents in the absence, but not in the presence, of 2-HE. In cell-attached membrane patches, 25 or 50 mM HCO₃^– in the bath markedly increased the product of channel number and open probability of CFTR, and this activation was attenuated by 2-HE. These findings demonstrate that sAC signaling pathway is involved in the regulation of CFTR function in human airway epithelium and thereby provides a link between the level of intracellular HCO₃^–/CO₂ and the modulation of HCO₃^–-conductive CFTR function by cAMP/PKA.

cystic fibrosis transmembrane conductance regulator; bicarbonate; adenosine 3',5'-cyclic monophosphate; 2-hydroxyestradiol

This article has been cited by other articles:

				S. W. Moore, K. Lai Wing Sun, F. Xie, P. A. Barker, M. Conti, and T. E. Kennedy Soluble Adenylyl Cyclase Is Not Required for Axon Guidance to Netrin-1 J. Neurosci., April 9, 2008; 28(15): 3920 - 3924. [Abstract] [Full Text] [PDF]

				A. Schmid, Z. Sutto, M.-C. Nlend, G. Horvath, N. Schmid, J. Buck, L. R. Levin, G. E. Conner, N. Fregien, and M. Salathe Soluble Adenylyl Cyclase Is Localized to Cilia and Contributes to Ciliary Beat Frequency Regulation via Production of cAMP J. Gen. Physiol., July 1, 2007; 130(1): 99 - 109. [Abstract] [Full Text] [PDF]