The essential role of luminal BK channels in distal colonic K⁺ secretion

Beskrivelse

Distal colonic K⁺ excretion is determined by the balance of K⁺ absorption and K⁺ secretion by the enterocytes. This presentation summarizes the current knowledge of the cellular mechanism for colonic K⁺ secretion, with focus on the luminal secretory K⁺ channel. Several recent observations highlight a pivotal role of the large conductance, Ca²⁺-activated K_Ca1.1 (BK, KCNM) channel as the functionally relevant luminal K⁺ efflux pathway in mouse distal colon (1, 2). This conclusion was based on clear cut results from BK knock-out mice. Several relevant issues will be presented: 1. BK channels mediate the resting distal colonic K⁺ secretion, 2. they are acutely stimulated by luminal nucleotide receptor activation and an intracellular Ca²⁺ increase, 3. BK channels are regulated by aldosterone, 4. the cAMP-stimulated distal colonic K⁺ secretion is apparently mediated via BK channels, 5. and finally aldosterone was found to specifically up-regulate 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.

Literature Cited

   1.   Sausbier M, Matos JE, Sausbier U, Beranek G, Arntz C et al. 2006. Distal Colonic K⁺ Secretion Occurs via BK Channels J Am Soc Nephrol 17:1275-82

   2.   Sorensen MV, Matos JE, Sausbier M, Sausbier U, Ruth P et al. 2008. Aldosterone increases K_Ca1.1 (BK)-channel-mediated colonic K⁺ secretion J Physiol 586:4251-64