Regulation of Ion Transport in Colonic Crypts

Greger, R.; Bleich, Markus; Leipziger, Jens; Ecke, D; Mall, Marcus; Kunzelmann, Karl

doi:10.1152/physiologyonline.1997.12.2.62

Cited by 65 publications

(82 citation statements)

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“…It is interesting that the resting I sc in the presence of luminal amiloride is significantly larger in BK Ϫ/Ϫ mice. In the absence of K ϩ secretion and Na ϩ absorption, an increased I sc value is a strong indicator for an elevated NaCl secretion (30). It therefore is suggested that this increased NaCl secretion is the cause of colonic Na ϩ wasting in BK Ϫ/Ϫ mice, but other undiscovered factors may be involved, such as a higher delivery of Na ϩ from more proximal parts of the intestine.…”

Section: Altered Fecal K ϩ and Na ϩ Contentmentioning

confidence: 99%

Distal Colonic K+ Secretion Occurs via BK Channels

Sausbier¹,

Matos²,

Sausbier³

et al. 2006

Journal of the American Society of Nephrology

108

125

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K؉ secretion in the kidney and distal colon is a main determinant of K ؉ homeostasis. This study investigated the identity of the relevant luminal secretory K ؉ ion channel in distal colon. An Ussing chamber was used to measure ion transport in the recently generated BK channel-deficient (BK ؊ -activated K ϩ channel, i.e., of small, intermediate, or large conductance (9,10). In some epithelia, including rodent colon, evidence indicates that BK channels (large conductance) localize to the luminal membrane (11,12). We therefore considered the BK channel as the first-choice candidate. This also was suggested in a previous work that showed that luminal iberiotoxin, a specific blocker for BK (large conductance) channels, was able to inhibit strongly the luminal nucleotide-triggered K / Materials and Methods MiceThe previously generated BK Ϫ/Ϫ and wild-type (WT) littermate mice on hybrid 129Sv/C57BL6 background were used (F2 generation) (13). Generation of SK4 channel-deficient (SK4 Ϫ/Ϫ ) mice was as follows:Using a genomic 129/ola cosmid library (RZPD), the targeting vector was constructed such that the pore exon was flanked by a single loxP site and a floxed neo/tk cassette. This construct was electroporated into R1 embryonic stem (ES) cells, and G418-resistant clones were screened. Two positive clones, analyzed by Southern blotting, were transiently transfected with a Cre-expressing plasmid to excise the neo/tk cassette and the pore exon yielding L1/ϩ clones. Correctly targeted L1/ϩ clones were

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Section: Altered Fecal K ϩ and Na ϩ Contentmentioning

confidence: 99%

Distal Colonic K+ Secretion Occurs via BK Channels

Sausbier¹,

Matos²,

Sausbier³

et al. 2006

Journal of the American Society of Nephrology

108

125

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“…A typical secretory agonist such as PGE 2 elevates cAMP, which activates luminal CFTR and basolateral KCNQ1/KCNE3 channels (11). In contrast, activation of muscarinic receptors increases [Ca 2+ ] i and activates SK4 channels to elevate the driving force for Cl -exit (13).…”

mentioning

confidence: 99%

P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport

Köttgen

Löffler²,

Jacobi³

et al. 2003

J. Clin. Invest.

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“…Basolateral K + channels are mandatory for Cl -secretion (Greger et al, 1997); so far, two classes of K + channels have been identified. Both types take part in Cl -secretion in rat colon: Ca 2+ -dependent rSK4 channels (Warth et al, 1999) and cyclic AMP-activated KCNQ1/KCNE3 channels (Schroeder et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Basolateral Ca²⁺‐dependent K⁺‐channels play a key role in Cl—secretion induced by taurodeoxycholate from colon mucosa

Moschetta

Portincasa

Debellis

et al. 2003

Biology of the Cell

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The diarrhea associated with malabsorption of bile salts such as the secondary hydrophobic taurodeoxycholate (TDC) may be partly explained by the TDC-induced increase in colon Cl -secretion. We, therefore, investigated the effects of TDC (0.5-8 mM) on electrical parameters and electrolyte transport of rat proximal colon mucosa mounted in Ussing chambers. Colonic secretion, measured as short circuit current (I SC ), progressively increased on mucosal incubation with TDC ranging 0.5-2 mM; up to TDC 2 mM, a spontaneous recovery toward control values with no changes in epithelial resistance (Rt), and lactate dehydrogenase (LDH) release was observed. In contrast, for TDC > 2 mM, I SC increased further and the effect was progressive and associated with a significant decrease in the Rt and increased LDH release, implying a cytolytic effect. Mucosal preincubation with the Cl -channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), fully prevented the precytolytic effect of TDC on I SC . Serosal preincubation with furosemide, a Na + /K + /2Cl -cotransporter inhibitor, significantly reduced TDC-induced increase in I SC . Inhibition of the basolateral Ca 2+ -dependent K + channel-rSK4-with serosal clotrimazole or incubation with mucosal Ca 2+ -free (EGTA) buffer completely prevented precytolytic TDC-induced increase in I SC . In conclusion, Cl -secretion is activated in colon mucosa by TDC low concentrations; while at higher concentrations, a detergent cytotoxic effect intervenes. Activation of the Ca 2+ -dependent basolateral K + pathway, through TDC-induced apical Ca 2+ influx, provides the Na + /K + /2Cl -basolateral activation, thereby the driving force for the apical exit of Cl -ions. These findings further enhance the knowledge of the pathogenic mechanisms of diarrhea associated with bile salt malabsorption.

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Regulation of Ion Transport in Colonic Crypts

Cited by 65 publications

References 0 publications

Distal Colonic K+ Secretion Occurs via BK Channels

Distal Colonic K+ Secretion Occurs via BK Channels

P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport

Basolateral Ca²⁺‐dependent K⁺‐channels play a key role in Cl—secretion induced by taurodeoxycholate from colon mucosa

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Regulation of Ion Transport in Colonic Crypts

Cited by 65 publications

References 0 publications

Distal Colonic K+ Secretion Occurs via BK Channels

Distal Colonic K+ Secretion Occurs via BK Channels

P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport

Basolateral Ca2+‐dependent K+‐channels play a key role in Cl—secretion induced by taurodeoxycholate from colon mucosa

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Basolateral Ca²⁺‐dependent K⁺‐channels play a key role in Cl—secretion induced by taurodeoxycholate from colon mucosa