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Bradykinin regulation of salt transport across mouse inner medullary collecting duct epithelium involves activation of a Ca2+ -dependent Cl- conductance

Lookup NU author(s): Dr Michael Gray, Dr Colin Brown, Professor Nicholas Simmons


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1. The mechanism by which bradykinin regulates renal epithelial salt transport has been investigated using a mouse inner medullary renal collecting duct cell-line mIMCD-K2. 2. Using fura-2 loaded mIMCD-K2 cells bradykinin (100 nM) has been shown to induce a transient increase in intracellular Ca2+ via activation of bradykinin B2 receptors localized to both the apical and basolateral epithelial cell surfaces. 3. In mIMCD-K2 epithelial cell-layers clamped in Ussing chambers, 100 nM bradykinin via apical and basolateral bradykinin B2 receptors stimulated a transient increase in inward short-circuit current (Isc) of similar duration to the increase in intracellular Ca2+. 4. Replacements of the bathing solution Na+ by the impermeant cation, N-methyl-D-glucamine and of Cl- and HCO3- by the impermeant anion gluconate at either the apical (no reduction) or basal bathing solutions (abolition of the response) are consistent with the bradykinin-stimulated increase in inward Isc resulting from basal to apical Cl- (anion) secretion. 5. Using the slow whole cell configuration of the patch-clamp technique, bradykinin was shown to activate a transient Cl- selective whole cell current which showed time-dependent activation at positive membrane potentials and time-dependent inactivation at negative membrane potentials. These currents were distinct from those activated by forskolin (CFTR), but identical to those activated by exogenous ATP and are therefore consistent with bradykinin activation of a Ca2+-dependent Cl- conductance. 6. The molecular identity of the Ca2+-dependent Cl- conductance has been investigated by an RT-PCR approach. Expression of an mRNA transcript with 96% identity to mCLCA1/2 was confirmed, however an additional but distinct mRNA transcript with only 81% of the identity to mCLCA1/2 was identified.

Publication metadata

Author(s): Brown CDA; Gray MA; Simmons NL; Kose H; Boese SH; Glanville M

Publication type: Article

Publication status: Published

Journal: British Journal of Pharmacology

Year: 2000

Volume: 131

Issue: 8

Pages: 1689-1699

ISSN (print): 0007-1188

ISSN (electronic): 1476-5381

Publisher: John Wiley & Sons


DOI: 10.1038/sj.bjp.0703749

PubMed id: 11139448


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