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.
Chronic dietary K+ loading stimulates an active K+ secretory process in rat distal colon, which involves an increase in the macroscopic apical K+ conductance of surface epithelial cells. In the present study, the abundance and characteristics of K+ channels constituting this enhanced apical K+ conductance were evaluated using patch clamp recording techniques.2. In isolated non‐polarized surface cells, K+ channels were seen in 9 of 90 (10%) cell‐attached patches in cells from control animals, and in 247 of 437 (57%) cell‐attached patches in cells from K+‐loaded animals, with a significant (P < 0.001) shift in distribution density. Similarly, recordings from cell‐attached patches of the apical membrane of surface cells surrounding the openings of distal colonic crypts revealed identical K+ channels in 1 of 11 (9%) patches in control animals, and in 9 of 13 (69%) patches in K+‐loaded animals.
In isolated surface cells and surface cells in situ, K+ channels had mean slope conductances of 209 ± 6 and 233 ± 14 pS, respectively, when inside‐out patches were bathed symmetrically in K2SO4 solution. The channels were sensitive to ‘cytosolic’ Ca2+ concentration, were voltage sensitive at ‘cytosolic’ Ca2+ concentrations encountered in colonic epithelial cells, and were inhibited by 1 mm quinidine, 20 mm TEA or 5 mm Ba2+ ions.
The data show that dietary K+ loading increases the abundance of Ca2+‐ and voltage‐sensitive large‐conductance K+ channels in the apical membrane of surface cells in rat distal colon. These channels constitute the enhanced macroscopic apical K+ conductance previously identified in these cells, and are likely to play a critical role in the active K+ secretory process that typifies this model of colonic K+ adaptation.
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