Secretory modulation of basolateral membrane inwardly  rectified K<sup>+</sup> channel in guinea pig distal colonic crypts

Li, Yingjun; Halm, Dan R.

doi:10.1152/ajpcell.00065.2001

Cited by 45 publications

(29 citation statements)

References 54 publications

(104 reference statements)

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“…Because K Ca 3.1 was likely not required during these secretory modes, other K ϩ channel types must be involved in the responses. The inwardly rectified K ϩ channel observed in the basolateral membrane of guinea pig distal colonic crypts (with a singlechannel conductance similar to K Ca 3.1) was stimulated by either forskolin or CCh but was insensitive to changes in Ca 2ϩ activity on the cytoplasmic side contrary to the expectation for K Ca 3.1 (40); the molecular identity of this channel is presently unknown. The group of channels involved was defined further by sensitivity to the inhibitors clofilium and E-4031.…”

Section: Discussionmentioning

confidence: 84%

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Distinct K⁺ conductive pathways are required for Cl⁻ and K⁺ secretion across distal colonic epithelium

Halm¹,

Liao²,

Halm³

2006

American Journal of Physiology-Cell Physiology

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Secretion of Cl(-) and K(+) in the colonic epithelium operates through a cellular mechanism requiring K(+) channels in the basolateral and apical membranes. Transepithelial current [short-circuit current (I(sc))] and conductance (G(t)) were measured for isolated distal colonic mucosa during secretory activation by epinephrine (Epi) or PGE(2) and synergistically by PGE(2) and carbachol (PGE(2) + CCh). TRAM-34 at 0.5 microM, an inhibitor of K(Ca)3.1 (IK, Kcnn4) K(+) channels (H. Wulff, M. J. Miller, W. Hänsel, S. Grissmer, M. D. Cahalan, and K. G. Chandy. Proc Natl Acad Sci USA 97: 8151-8156, 2000), did not alter secretory I(sc) or G(t) in guinea pig or rat colon. The presence of K(Ca)3.1 in the mucosa was confirmed by immunoblot and immunofluorescence detection. At 100 microM, TRAM-34 inhibited I(sc) and G(t) activated by Epi ( approximately 4%), PGE(2) ( approximately 30%) and PGE(2) + CCh ( approximately 60%). The IC(50) of 4.0 microM implicated involvement of K(+) channels other than K(Ca)3.1. The secretory responses augmented by the K(+) channel opener 1-EBIO were inhibited only at a high concentration of TRAM-34, suggesting further that K(Ca)3.1 was not involved. Sensitivity of the synergistic response (PGE(2) + CCh) to a high concentration TRAM-34 supported a requirement for multiple K(+) conductive pathways in secretion. Clofilium (100 microM), a quaternary ammonium, inhibited Cl(-) secretory I(sc) and G(t) activated by PGE(2) ( approximately 20%) but not K(+) secretion activated by Epi. Thus Cl(-) secretion activated by physiological secretagogues occurred without apparent activity of K(Ca)3.1 channels but was dependent on other types of K(+) channels sensitive to high concentrations of TRAM-34 and/or clofilium.

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Section: Discussionmentioning

confidence: 84%

“…Several types of K ϩ channels have been detected in colonic epithelial cells (23,40,60,71,72). Two of these types have been proposed to support cAMP-and Ca 2ϩ -activated secretion, K V 7.1 (K V LQT1, Kcnq1) and K Ca 3.1 (IK1, SK4, Kcnn4), respectively (23).…”

mentioning

confidence: 99%

Distinct K⁺ conductive pathways are required for Cl⁻ and K⁺ secretion across distal colonic epithelium

Halm¹,

Liao²,

Halm³

2006

American Journal of Physiology-Cell Physiology

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“…Total RNA was extracted by RNeasy-Mini-Kit (Qiagen, Valencia, CA) from isolated mucosa and EDTA-released epithelial cells (38). Individual crypts were dissected under 40ϫ magnification with Dumont no.…”

Section: Methodsmentioning

confidence: 99%

Role of the BK channel (K_Ca1.1) during activation of electrogenic K⁺ secretion in guinea pig distal colon

Zhang

Halm

2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Secretagogues acting at a variety of receptor types activate electrogenic K(+) secretion in guinea pig distal colon, often accompanied by Cl(-) secretion. Distinct blockers of K(Ca)1.1 (BK, Kcnma1), iberiotoxin (IbTx), and paxilline inhibited the negative short-circuit current (I(sc)) associated with K(+) secretion. Mucosal addition of IbTx inhibited epinephrine-activated I(sc) ((epi)I(sc)) and transepithelial conductance ((epi)G(t)) consistent with K(+) secretion occurring via apical membrane K(Ca)1.1. The concentration dependence of IbTx inhibition of (epi)I(sc) yielded an IC(50) of 193 nM, with a maximal inhibition of 51%. Similarly, IbTx inhibited (epi)G(t) with an IC(50) of 220 nM and maximal inhibition of 48%. Mucosally added paxilline (10 μM) inhibited (epi)I(sc) and (epi)G(t) by ∼50%. IbTx and paxilline also inhibited I(sc) activated by mucosal ATP, supporting apical K(Ca)1.1 as a requirement for this K(+) secretagogue. Responses to IbTx and paxilline indicated that a component of K(+) secretion occurred during activation of Cl(-) secretion by prostaglandin-E(2) and cholinergic stimulation. Analysis of K(Ca)1.1α mRNA expression in distal colonic epithelial cells indicated the presence of the ZERO splice variant and three splice variants for the COOH terminus. The presence of the regulatory β-subunits K(Ca)β1 and K(Ca)β4 also was demonstrated. Immunolocalization supported the presence of K(Ca)1.1α in apical and basolateral membranes of surface and crypt cells. Together these results support a cellular mechanism for electrogenic K(+) secretion involving apical membrane K(Ca)1.1 during activation by several secretagogue types, but the observed K(+) secretion likely required the activity of additional K(+) channel types in the apical membrane.

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“…Thus a comparison of these two modes of secretion in these species can be used to demonstrate the varied roles of basolateral membrane K ϩ channels. In particular, increased basolateral membrane K ϩ channel activity would aid Cl Ϫ secretion by enhancing the electrochemical driving force for conductive apical Cl Ϫ exit, whereas decreased activity could increase K ϩ secretion by limiting basolateral exit of K ϩ into the interstitial space (40). The focus of this study was to examine the epithelial location of Kcnq1/Kcne3 K ϩ channels in the colon and to use the chromanol derivative HMR1556 (22) to determine the involvement of this K ϩ channel type in secretory activation by physiological secretagogues.…”

mentioning

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K⁺ channel K_VLQT1 located in the basolateral membrane of distal colonic epithelium is not essential for activating Cl⁻ secretion

Liao

Wang²,

Halm³

et al. 2005

American Journal of Physiology-Cell Physiology

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The cellular mechanism for Cl(-) and K(+) secretion in the colonic epithelium requires K(+) channels in the basolateral and apical membranes. Colonic mucosa from guinea pig and rat were fixed, sectioned, and then probed with antibodies to the K(+) channel proteins K(V)LQT1 (Kcnq1) and minK-related peptide 2 (MiRP2, Kcne3). Immunofluorescence labeling for Kcnq1 was most prominent in the lateral membrane of crypt cells in rat colon. The guinea pig distal colon had distinct lateral membrane immunoreactivity for Kcnq1 in crypt and surface cells. In addition, Kcne3, an auxiliary subunit for Kcnq1, was detected in the lateral membrane of crypt and surface cells in guinea pig distal colon. Transepithelial short-circuit current (I(sc)) and transepithelial conductance (G(t)) were measured for colonic mucosa during secretory activation by epinephrine (EPI), prostaglandin E(2) (PGE(2)), and carbachol (CCh). HMR1556 (10 microM), an inhibitor of Kcnq1 channels (Gerlach U, Brendel J, Lang HJ, Paulus EF, Weidmann K, Brüggemann A, Busch A, Suessbrich H, Bleich M, and Greger R. J Med Chem 44: 3831-3837, 2001), partially (approximately 50%) inhibited Cl(-) secretory I(sc) and G(t) activated by PGE(2) and CCh in rat colon with an IC(50) of 55 nM, but in guinea pig distal colon Cl(-) secretory I(sc) and G(t) were unaltered. EPI-activated K(+)-secretory I(sc) and G(t) also were essentially unaltered by HMR1556 in both rat and guinea pig colon. Although immunofluorescence labeling with a Kcnq1 antibody supported the basolateral membrane presence in colonic epithelium of the guinea pig as well as the rat, the Kcnq1 K(+) channel is not an essential component for producing Cl(-) secretion. Other K(+) channels present in the basolateral membrane presumably must also contribute directly to the K(+) conductance necessary for K(+) exit during activation of Cl(-) secretion in the colonic mucosa.

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Secretory modulation of basolateral membrane inwardly rectified K⁺ channel in guinea pig distal colonic crypts

Abstract: Li, Yingjun, and Dan R. Halm. Secretory modulation of basolateral membrane inwardly rectified K ϩ channel in guinea pig distal colonic crypts.

Cited by 45 publications

References 54 publications

Distinct K⁺ conductive pathways are required for Cl⁻ and K⁺ secretion across distal colonic epithelium

Distinct K⁺ conductive pathways are required for Cl⁻ and K⁺ secretion across distal colonic epithelium

Role of the BK channel (K_Ca1.1) during activation of electrogenic K⁺ secretion in guinea pig distal colon

K⁺ channel K_VLQT1 located in the basolateral membrane of distal colonic epithelium is not essential for activating Cl⁻ secretion

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Secretory modulation of basolateral membrane inwardly rectified K+ channel in guinea pig distal colonic crypts

Abstract: Li, Yingjun, and Dan R. Halm. Secretory modulation of basolateral membrane inwardly rectified K ϩ channel in guinea pig distal colonic crypts.

Cited by 45 publications

References 54 publications

Distinct K+ conductive pathways are required for Cl− and K+ secretion across distal colonic epithelium

Distinct K+ conductive pathways are required for Cl− and K+ secretion across distal colonic epithelium

Role of the BK channel (KCa1.1) during activation of electrogenic K+ secretion in guinea pig distal colon

K+ channel KVLQT1 located in the basolateral membrane of distal colonic epithelium is not essential for activating Cl− secretion

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Secretory modulation of basolateral membrane inwardly rectified K⁺ channel in guinea pig distal colonic crypts

Distinct K⁺ conductive pathways are required for Cl⁻ and K⁺ secretion across distal colonic epithelium

Distinct K⁺ conductive pathways are required for Cl⁻ and K⁺ secretion across distal colonic epithelium

Role of the BK channel (K_Ca1.1) during activation of electrogenic K⁺ secretion in guinea pig distal colon

K⁺ channel K_VLQT1 located in the basolateral membrane of distal colonic epithelium is not essential for activating Cl⁻ secretion