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


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

SUBMITTER: Bowley KA 

PROVIDER: S-EPMC1773689 | biostudies-literature | 2003 Jun

REPOSITORIES: biostudies-literature

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

Bowley K A KA   Morton M J MJ   Hunter M M   Sandle G I GI  

Gut 20030601 6


<h4>Background</h4>Aldosterone has a rapid, non-genomic, inhibitory effect on macroscopic basolateral K(+) conductance in the human colon, reducing its capacity for Cl(-) secretion. The molecular identity of the K(+) channels constituting this aldosterone inhibitable K(+) conductance is unclear.<h4>Aim</h4>To characterise the K(+) channel inhibited by aldosterone present in the basolateral membrane of human colonic crypt cells.<h4>Methods</h4>Crypts were isolated from biopsies of healthy sigmoid  ...[more]

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