Enhanced large intestinal potassium permeability in end-stage renal disease.
The capacity of the colon for potassium (K+) secretion increases in end-stage renal disease (ESRD), to the extent that it makes a substantial contribution to K+ homeostasis. This colonic K+ adaptive response may reflect enhanced active K+ secretion, and be associated with an increase in apical membrane K+ permeability. In this study, this hypothesis was tested in patients with normal renal function or ESRD, by evaluating the effect of barium ions (a K+ channel inhibitor) on rectal K+ secretion using a rectal dialysis technique, and the expression of high conductance (BK) K+ channel protein in colonic mucosa by immunohistochemistry. Under basal conditions, rectal K+ secretion was almost threefold greater (p < 0.02) in ESRD patients (n = 8) than in patients with normal renal function (n = 10). Intraluminal barium (5 mmol/l) decreased K+ secretion in the ESRD patients by 45% (p < 0.05), but had no effect on K+ transport in patients with normal renal function. Immunostaining using a specific antibody to the BK channel alpha-subunit revealed greater (p < 0.001) levels of BK channel protein expression in surface colonocytes and crypt cells in ESRD patients (n = 9) than in patients with normal renal function (n = 9), in whom low levels of expression were mainly restricted to surface colonocytes. In conclusion, these results suggest that enhanced colonic K+ secretion in ESRD involves an increase in the apical K+ permeability of the large intestinal epithelium, which most likely reflects increased expression of apical BK channels.
Mathialahan
T
T
Molecular Medicine Unit, St James's University Hospital, Leeds, UK.
Maclennan
K A
KA
Sandle
L N
LN
Verbeke
C
C
Sandle
G I
GI
D000328:Adult; D000368:Aged; D001464:Barium / Q000494:pharmacology; D016022:Case-Control Studies; D002412:Cations; D003956:Dialysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism*; D007420:Intestine, Large / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010539:Permeability; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000032:analysis / Q000378:metabolism; D012007:Rectum / Q000378:metabolism; D018709:Statistics, Nonparametric
D002412:Cations; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D001464:Barium; D011188:Potassium