The essential role of luminal BK channels in distal colonic K+ secretion.
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, Ca(2+)-activated K(Ca)1.1 (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 Ca(2+) (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 Ca(2+) and cAMP activation and long term aldosterone regulation.
Department of Physiology and Biophysics, Aarhus University, Aarhus, Denmark.
Mads V
MV
Sörensen
Jens
J
Leipziger
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000378:metabolism*
C465449:Kcnma1 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D000450:Aldosterone; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium