Sörensen, Mads V Aarhus University
Leipziger, Jens Aarhus University
Distal colonic K+ excretion is determined by the balance of K+ absorption and K+ secretion of the enterocytes. K+ secretion occurs via active basolateral K+ uptake mostly via the NKCC1 co-transporter followed by K+ exit via a luminal K+ channel. The specific focus here is directed towards the luminal secretory K+ channel (1). Several recent observations highlight the pivotal role of the large conductance, Ca2+-activated KCa1.1 (BK, KCNMA) channel as the only functionally relevant luminal K+ efflux pathway in mouse distal colon (2, 3). This conclusion was based on defining results from BK knock-out mice. The following key observations were made : 1. BK channels mediate the resting distal colonic K+ secretion (2, 4), 2. They are acutely stimulated by activation of luminal nucleotide receptor and elevations of intracellular Ca2+ (2, 4, 5), 3. Colonic BK channels are up-regulated by increases of plasma aldosterone (3), 4. In addition, the cAMP-stimulated distal colonic K+ secretion is apparently mediated via BK channels, 5. Finally, aldosterone was found to up-regulate specifically the ZERO (e.g. cAMP activated) C-terminal splice variant of the BK channel. In summary, we suggest that the sole exit pathway for transcellular K+ secretion in mammalian distal colon is the BK channel, which is the target for short term intracellular Ca2+ and cAMP activation and long term aldosterone regulation.
The Journal of Medical Investigation
Faculty of Medicine Tokushima University
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