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Differential regulation of large conductance K + (BK) channel mediated K + secretion in proximal and distal colon by aldosterone
Author(s) -
Nickerson Andrew J,
Galbreath Kyla M,
Rajendran Vazhaikkurichi M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1223.15
Subject(s) - chemistry , forskolin , endocrinology , aldosterone , medicine , apical membrane , secretion , ussing chamber , patch clamp , sodium–hydrogen antiporter , biology , sodium , biochemistry , receptor , stimulation , organic chemistry , membrane
Aldosterone (“aldo”) differentially regulates electrolyte transport processes, as it stimulates Na‐H exchanger isoform‐3 (NHE3) mediated electroneutral Na + absorption, and down‐regulates NHE3 and induces epithelial Na + channel (ENaC) mediated electrogenic Na + absorption in proximal and distal segments of rat colon, respectively. Electrogenic active K + secretion is present in proximal colon, while H + , K + ‐ATPase mediated electroneutral K + absorption is present in distal colon of normal rat colon. Aldo enhances H + , K + ‐ATPase expression and electroneutral K + absorption in distal colon. Mucosal ortho‐vanadate (VO 4 ; p‐type ATPase inhibitor) unmasked the “aldo” induced BK channel mediated K + secretion in distal colon. It is not known whether “aldo” also stimulates BK channel mediated active K + secretion in proximal colon. Studies were, therefore, initiated to identify whether “aldo” also activates K + secretion in proximal colon. Aldo rats were generated by feeding Na‐free diet for 6 – 7 days. 86 Rb (K + surrogate) fluxes were measured in muscularis stripped proximal colon mounted under voltage clamp condition in Ussing chamber. Mucosal to serosal (m‐s) and serosal to mucosal (s‐m) fluxes were measured, while net fluxes were calculated by subtracting s‐m from m‐s. Net positive and negative fluxes represent active absorption and secretion, respectively. Aldo significantly enhanced K + secretion (−0.25 ± 0.05 vs −0.47 ± 0.12 μEq/h.cm2; p < 0.05). Forskolin (FSK, adenylate kinase activator) stimulated K + secretion in both normal (0.25 ± 0.05 vs 0.42 ± 0.09 μEq/h.cm2; p < 0.05) and aldo (0.47 ± 0.12 vs 1.30 ± 0.12 μEq/h.cm2). Mucosal iberiotoxin (IbTX, BK channel inhibitor) inhibited FSK‐stimulated K + secretion in normal, but it did not affect FSK‐stimulated K + secretion in aldo proximal colon. In contrast to IbTX, mucosal charybdotoxin [CTX; intermediate K + (IK) channel blocker) completely inhibited the FSK‐stimulated K + secretion in aldo proximal. We conclude that FKS stimulates active K + secretion via: 1) both BK and IK channels in normal proximal colon; and 2) entirely through IK channels in proximal colon. Support or Funding Information This work was supported by NIH NIDDK Grant 1006856R to VMR.