Abolition of Ca2+-mediated intestinal anion secretion and increased stool dehydration in mice lacking the intermediate conductance Ca2+-dependent K+ channel Kcnn4

Flores, CA; Melvin, JE; Figueroa, CD; Sepulveda, FV

Abstract

Intestinal fluid secretion is driven by apical membrane, cystic fibrosis transmembrane conductance regulator (CFTR)-mediated efflux of Cl- that is concentrated in cells by basolateral Na+-K+ - 2Cl- cotransporters (NKCC1). An absolute requirement for Cl- efflux is the parallel activation of KK+ channels which maintain a membrane potential that sustains apical anion secretion. Both cAMP and Ca2+ are intracellular signals for intestinal Cl- secretion. The KK+ channel involved in cAMP-dependent secretion has been identified as the KCNQ1-KCNE3 complex, but the identity of the K+ channel driving Ca2+-activated Cl-secretion is controversial. We have now used a Kcnn4 null mouse to show that the intermediate conductance IK1 K+ channel is necessary and sufficient to support Ca2+-dependent Cl- secretion in large and small intestine. Ussing chambers were used to monitor transepithelial potential, resistance and equivalent short-circuit current in colon and jejunum from control and Kcnn4 null mice. Na+, K+ and water content of stools was also measured. Distal colon and small intestinal epithelia from Kcnn4 null mice had normal cAMP-dependent Cl- secretory responses. In contrast, they completely lacked Cl- secretion in response to Ca+-mobilizing agonists. Ca2+-activated electrogenic K+ secretion was increased in colon epithelium of mice deficient in the IK1 channel. Na+ and water content of stools was diminished in IK1-null animals. The use of Kcnn4 null mice has allowed us to demonstrate that IK1 K+ channels are solely responsible for driving intestinal Ca2+-activated Cl-secretion. The absence of this channel leads to a marked reduction in water content in the stools, probably as a consequence of decreased electrolyte and water secretion. © 2007 The Authors. Journal compilation © 2007 The Physiological Society.

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Título según WOS: Abolition of Ca2+-mediated intestinal anion secretion and increased stool dehydration in mice lacking the intermediate conductance Ca2+-dependent K+ channel Kcnn4
Título según SCOPUS: Abolition of Ca2+-mediated intestinal anion secretion and increased stool dehydration in mice lacking the intermediate conductance Ca2+-dependent K+ channel Kcnn4
Título de la Revista: JOURNAL OF PHYSIOLOGY-LONDON
Volumen: 583
Número: 2
Editorial: Wiley
Fecha de publicación: 2007
Página de inicio: 705
Página final: 717
Idioma: English
URL: http://www.jphysiol.org/cgi/doi/10.1113/jphysiol.2007.134387
DOI:

10.1113/jphysiol.2007.134387

Notas: ISI, SCOPUS