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Non-genomic regulation of intermediate conductance potassium channels by aldosterone in human colonic crypt cells\ud \ud

By K.A. Bowley, M.J. Morton, M. Hunter and G.I. Sandle

Abstract

BACKGROUND: Aldosterone has a rapid, non-genomic, inhibitory effect on macroscopic basolateral K+\ud conductance in the human colon, reducing its capacity for Cl− secretion. The molecular identity of the\ud K+ channels constituting this aldosterone inhibitable K+ conductance is unclear.\ud \ud AIM: To characterise the K+ channel inhibited by aldosterone present in the basolateral membrane of\ud human colonic crypt cells.\ud \ud METHODS: Crypts were isolated from biopsies of healthy sigmoid colon obtained during colonoscopy.\ud The effect of aldosterone on basolateral K+ channels, and the possible involvement of Na+:H+ exchange,\ud were studied by patch clamp techniques. Total RNA from isolated crypts was subjected to reverse\ud transcriptase-polymerase chain reaction (RT-PCR) using primers specific to intermediate conductance\ud K+ channels (KCNN4) previously identified in other human tissues.\ud \ud RESULTS: In cell attached patches, 1 nmol/l aldosterone significantly decreased the activity of intermediate\ud conductance (27 pS) K+ channels by 31%, 53%, and 54% after 1, 5 and 10, minutes, respectively.\ud Increasing aldosterone concentration to 10 nmol/l produced a further 56% decrease in channel\ud activity after five minutes. Aldosterone 1–10 nmol/l had no effect on channel activity in the presence of\ud 20 µmol/l ethylisopropylamiloride, an inhibitor of Na+:H+ exchange. RT-PCR identified KCNN4\ud mRNA, which is likely to encode the 27 pS K+ channel inhibited by aldosterone.\ud \ud CONCLUSION: Intermediate conductance K+ channels (KCNN4) present in the basolateral membranes of\ud human colonic crypt cells are a target for the non-genomic inhibitory effect of aldosterone, which\ud involves stimulation of Na+:H+ exchange, thereby reducing the capacity of the colon for Cl− secretion

Year: 2003
OAI identifier: oai:eprints.whiterose.ac.uk:229

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