Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning
Standard
Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles. / Jepps, Thomas Andrew; Greenwood, Iain A; Moffatt, James D; Sanders, Kenton M; Ohya, Susumu.
I: A J P: Gastrointestinal and Liver Physiology (Online), Bind 297, Nr. 1, 07.2009, s. G107-15.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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
VL - 297
SP - G107-15
JO - A J P: Gastrointestinal and Liver Physiology (Online)
JF - A J P: Gastrointestinal and Liver Physiology (Online)
SN - 1522-1547
IS - 1
ER -
ID: 108539609