Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles

Thomas Andrew Jepps; Iain A Greenwood; James D Moffatt; Kenton M Sanders; Susumu Ohya

doi:10.1152/ajpgi.00057.2009

Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles

Thomas Andrew Jepps, Iain A Greenwood, James D Moffatt, Kenton M Sanders, Susumu Ohya

Physiology of circulation, kidney and lung

54 Citations (Scopus)

Abstract

Members of the K(v)7 voltage-gated K(+) channel family are important determinants of cardiac and neuronal membrane excitability. Recently, we and others have shown that K(v)7 channels are also crucial regulators of smooth muscle activity. The aim of the present study was to assess the K(v)7 expression in different parts of the murine gastrointestinal (GI) tract and to assess their functional roles by use of pharmacological agents. Of KCNQ/K(v)7 members, both KCNQ4/K(v)7.4 and KCNQ5/K(v)7.5 genes and proteins were the most abundantly expressed K(v)7 channels in smooth muscles throughout the GI tract. Immunohistochemical staining also revealed that K(v)7.4 and K(v)7.5 but not K(v)7.1 were expressed in the circular muscle layer of the colon. In segments of distal colon circular muscle exhibiting spontaneous phasic contractions, the nonselective K(v)7 blockers XE991 and linopirdine increased the integral of tension. Increases in the integral of tension were also observed under conditions of neuronal blockade. Similar effects, although less marked, were observed in the proximal colon. As expected, the K(v)7.1-selective blocker chromanol 293B had no effect in either type of segment. These data show that K(v)7.x especially K(v)7.4 and K(v)7.5 are expressed in different regions of the murine gastrointestinal tract and blockers of K(v)7 channels augment inherent contractile activity. Drugs that selectively block K(v)7.4/7.5 might be promising therapeutics for the treatment of motility disorders such as constipation associated with irritable bowel syndrome.

Original language	English
Journal	A J P: Gastrointestinal and Liver Physiology (Online)
Volume	297
Issue number	1
Pages (from-to)	G107-15
ISSN	1522-1547
DOIs	https://doi.org/10.1152/ajpgi.00057.2009
Publication status	Published - Jul 2009

Keywords

Animals
Anthracenes
Blotting, Western
Carbamates
Chromans
Colon
Gastrointestinal Tract
Immunohistochemistry
Indoles
KCNQ Potassium Channels
KCNQ1 Potassium Channel
Mice
Mice, Inbred BALB C
Muscle Contraction
Muscle, Smooth
Myography
Phenylenediamines
Potassium Channel Blockers
Pyridines
Reverse Transcriptase Polymerase Chain Reaction
Sulfonamides

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10.1152/ajpgi.00057.2009

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title = "Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles",

abstract = "Members of the K(v)7 voltage-gated K(+) channel family are important determinants of cardiac and neuronal membrane excitability. Recently, we and others have shown that K(v)7 channels are also crucial regulators of smooth muscle activity. The aim of the present study was to assess the K(v)7 expression in different parts of the murine gastrointestinal (GI) tract and to assess their functional roles by use of pharmacological agents. Of KCNQ/K(v)7 members, both KCNQ4/K(v)7.4 and KCNQ5/K(v)7.5 genes and proteins were the most abundantly expressed K(v)7 channels in smooth muscles throughout the GI tract. Immunohistochemical staining also revealed that K(v)7.4 and K(v)7.5 but not K(v)7.1 were expressed in the circular muscle layer of the colon. In segments of distal colon circular muscle exhibiting spontaneous phasic contractions, the nonselective K(v)7 blockers XE991 and linopirdine increased the integral of tension. Increases in the integral of tension were also observed under conditions of neuronal blockade. Similar effects, although less marked, were observed in the proximal colon. As expected, the K(v)7.1-selective blocker chromanol 293B had no effect in either type of segment. These data show that K(v)7.x especially K(v)7.4 and K(v)7.5 are expressed in different regions of the murine gastrointestinal tract and blockers of K(v)7 channels augment inherent contractile activity. Drugs that selectively block K(v)7.4/7.5 might be promising therapeutics for the treatment of motility disorders such as constipation associated with irritable bowel syndrome.",

keywords = "Animals, Anthracenes, Blotting, Western, Carbamates, Chromans, Colon, Gastrointestinal Tract, Immunohistochemistry, Indoles, KCNQ Potassium Channels, KCNQ1 Potassium Channel, Mice, Mice, Inbred BALB C, Muscle Contraction, Muscle, Smooth, Myography, Phenylenediamines, Potassium Channel Blockers, Pyridines, Reverse Transcriptase Polymerase Chain Reaction, Sulfonamides",

author = "Jepps, {Thomas Andrew} and Greenwood, {Iain A} and Moffatt, {James D} and Sanders, {Kenton M} and Susumu Ohya",

year = "2009",

month = jul,

doi = "10.1152/ajpgi.00057.2009",

language = "English",

volume = "297",

pages = "G107--15",

journal = "American Journal of Physiology - Gastrointestinal and Liver Physiology",

issn = "1522-1547",

publisher = "American Physiological Society",

number = "1",

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TY - JOUR

T1 - Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles

AU - Jepps, Thomas Andrew

AU - Greenwood, Iain A

AU - Moffatt, James D

AU - Sanders, Kenton M

AU - Ohya, Susumu

PY - 2009/7

Y1 - 2009/7

N2 - Members of the K(v)7 voltage-gated K(+) channel family are important determinants of cardiac and neuronal membrane excitability. Recently, we and others have shown that K(v)7 channels are also crucial regulators of smooth muscle activity. The aim of the present study was to assess the K(v)7 expression in different parts of the murine gastrointestinal (GI) tract and to assess their functional roles by use of pharmacological agents. Of KCNQ/K(v)7 members, both KCNQ4/K(v)7.4 and KCNQ5/K(v)7.5 genes and proteins were the most abundantly expressed K(v)7 channels in smooth muscles throughout the GI tract. Immunohistochemical staining also revealed that K(v)7.4 and K(v)7.5 but not K(v)7.1 were expressed in the circular muscle layer of the colon. In segments of distal colon circular muscle exhibiting spontaneous phasic contractions, the nonselective K(v)7 blockers XE991 and linopirdine increased the integral of tension. Increases in the integral of tension were also observed under conditions of neuronal blockade. Similar effects, although less marked, were observed in the proximal colon. As expected, the K(v)7.1-selective blocker chromanol 293B had no effect in either type of segment. These data show that K(v)7.x especially K(v)7.4 and K(v)7.5 are expressed in different regions of the murine gastrointestinal tract and blockers of K(v)7 channels augment inherent contractile activity. Drugs that selectively block K(v)7.4/7.5 might be promising therapeutics for the treatment of motility disorders such as constipation associated with irritable bowel syndrome.

AB - Members of the K(v)7 voltage-gated K(+) channel family are important determinants of cardiac and neuronal membrane excitability. Recently, we and others have shown that K(v)7 channels are also crucial regulators of smooth muscle activity. The aim of the present study was to assess the K(v)7 expression in different parts of the murine gastrointestinal (GI) tract and to assess their functional roles by use of pharmacological agents. Of KCNQ/K(v)7 members, both KCNQ4/K(v)7.4 and KCNQ5/K(v)7.5 genes and proteins were the most abundantly expressed K(v)7 channels in smooth muscles throughout the GI tract. Immunohistochemical staining also revealed that K(v)7.4 and K(v)7.5 but not K(v)7.1 were expressed in the circular muscle layer of the colon. In segments of distal colon circular muscle exhibiting spontaneous phasic contractions, the nonselective K(v)7 blockers XE991 and linopirdine increased the integral of tension. Increases in the integral of tension were also observed under conditions of neuronal blockade. Similar effects, although less marked, were observed in the proximal colon. As expected, the K(v)7.1-selective blocker chromanol 293B had no effect in either type of segment. These data show that K(v)7.x especially K(v)7.4 and K(v)7.5 are expressed in different regions of the murine gastrointestinal tract and blockers of K(v)7 channels augment inherent contractile activity. Drugs that selectively block K(v)7.4/7.5 might be promising therapeutics for the treatment of motility disorders such as constipation associated with irritable bowel syndrome.

KW - Animals

KW - Anthracenes

KW - Blotting, Western

KW - Carbamates

KW - Chromans

KW - Colon

KW - Gastrointestinal Tract

KW - Immunohistochemistry

KW - Indoles

KW - KCNQ Potassium Channels

KW - KCNQ1 Potassium Channel

KW - Mice

KW - Mice, Inbred BALB C

KW - Muscle Contraction

KW - Muscle, Smooth

KW - Myography

KW - Phenylenediamines

KW - Potassium Channel Blockers

KW - Pyridines

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Sulfonamides

U2 - 10.1152/ajpgi.00057.2009

DO - 10.1152/ajpgi.00057.2009

M3 - Journal article

C2 - 19389803

SN - 1522-1547

VL - 297

SP - G107-15

JO - American Journal of Physiology - Gastrointestinal and Liver Physiology

JF - American Journal of Physiology - Gastrointestinal and Liver Physiology

IS - 1

ER -

Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles

Abstract

Keywords

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