F****n
发帖数: 438 | 1 那位大侠可以帮组查一下这几篇的全文吗？叩谢。
请发：y******[email protected].
I.
Role of small-conductance calcium-activated potassium channels in atrial
electrophysiology and fibrillation in the dog.
Qi XY1, Diness JG, Brundel BJ, Zhou XB, Naud P, Wu CT, Huang H, Harada M,
Aflaki M, Dobrev D, Grunnet M, Nattel S.
Author information
Abstract
BACKGROUND:
Recent evidence points to functional Ca2⁺-dependent K⁺ (SK)
channels in the heart that may govern atrial fibrillation (AF) risk, but the
underlying mechanisms are unclear. This study addressed the role of SK
channels in atrial repolarization and AF persistence in a canine AF model.
METHODS AND RESULTS:
Electrophysiological variables were assessed in dogs subjected to atrial
remodeling by 7-day atrial tachypacing (AT-P), as well as controls. Ionic
currents and single-channel properties were measured in isolated canine
atrial cardiomyocytes by patch clamp. NS8593, a putative selective SK
blocker, suppressed SK current with an IC₅₀ of ≈5 μmol/L,
without affecting Na⁺, Ca2⁺, or other K⁺ currents. Whole-
cell SK current sensitive to NS8593 was significantly larger in pulmonary
vein (PV) versus left atrial (LA) cells, without a difference in SK single-
channel open probability (P(o)), whereas AT-P enhanced both whole-cell SK
currents and single-channel P(o). SK-current block increased action
potential duration in both PV and LA cells after AT-P; but only in PV cells
in absence of AT-P. SK2 expression was more abundant at both mRNA and
protein levels for PV versus LA in control dogs, in both control and AT-P;
AT-P upregulated only SK1 at the protein level. Intravenous administration
of NS8593 (5 mg/kg) significantly prolonged atrial refractoriness and
reduced AF duration without affecting the Wenckebach cycle length, left
ventricular refractoriness, or blood pressure.
CONCLUSIONS:
SK currents play a role in canine atrial repolarization, are larger in PVs
than LA, are enhanced by atrial-tachycardia remodeling, and appear to
participate in promoting AF maintenance. These results are relevant to the
potential mechanisms underlying the association between SK single-nucleotide
polymorphisms and AF and suggest SK blockers as potentially interesting
anti-AF drugs.
KEYWORDS:
action potentials; anti-arrhythmia agents; electrophysiology; ion channels
II.
Small-conductance calcium-activated potassium (SK) channels contribute to
action potential repolarization in human atria
Lasse Skibsbye1,†, Claire Poulet2,†, Jonas Goldin Diness1,3, Bo
Hjorth Bentzen1,3,Lei Yuan1, Utz Kappert4, Klaus Matschke4, Erich Wettwer2,
Ursula Ravens2,Morten Grunnet3,*, Torsten Christ2,5 and Thomas Jespersen1
+
Author Affiliations
1Danish National Research Foundation Centre for Cardiac Arrhythmia,
Department of Biomedical Sciences, University of Copenhagen, Copenhagen,
Denmark
2Department of Pharmacology and Toxicology, Medical Faculty, Technical
University Dresden, Dresden, Germany
3Acesion Pharma ApS, Ole Maaløes Vej 3, Copenhagen DK-2200, Denmark
4Clinic for Cardiac Surgery, Heart Center Dresden, Medical Faculty, Dresden
University of Technology, Dresden, Germany
5Department of Experimental Pharmacology and Toxicology, University Medical
Center Hamburg-Eppendorf, Hamburg, Germany
↵*Corresponding author. Tel: +45 29336946; fax: +45 35327555, Email:
m*[email protected]
Received September 16, 2013.
Revision received April 2, 2014.
Accepted April 8, 2014.
Time for primary review: 27 days
Abstract
Aims Small-conductance calcium-activated potassium (SK) channels are
expressed in the heart of various species, including humans. The aim of the
present study was to address whether SK channels play a functional role in
human atria.
Methods and results Quantitative real-time PCR analyses showed higher
transcript levels of SK2 and SK3 than that of the SK1 subtype in human
atrial tissue. SK2 and SK3 were reduced in chronic atrial fibrillation (AF)
compared with sinus rhythm (SR) patients. Immunohistochemistry using
confocal microscopy revealed widespread expression of SK2 in atrial myocytes
. Two SK channel inhibitors (NS8593 and ICAGEN) were tested in heterologous
expression systems revealing ICAGEN as being highly selective for SK
channels, while NS8593 showed less selectivity for these channels. In
isolated atrial myocytes from SR patients, both inhibitors decreased
inwardly rectifying K+ currents by ～15% and prolonged action potential
duration (APD), but no effect was observed in myocytes from AF patients. In
trabeculae muscle strips from right atrial appendages of SR patients, both
compounds increased APD and effective refractory period, and depolarized the
resting membrane potential, while only NS8593 induced these effects in
tissue from AF patients. SK channel inhibition did not alter any
electrophysiological parameter in human interventricular septum tissue.
Conclusions SK channels are present in human atria where they participate in
repolarization. SK2 and SK3 were down-regulated and had reduced functional
importance in chronic AF. As SK current was not found to contribute
substantially to the ventricular AP, pharmacological inhibition of SK
channels may be a putative atrial-selective target for future antiarrhythmic
drug therapy.
III.
Expanding role of SK channels in cardiac electrophysiology.
Mahida S.
Author information
Abstract
The small conductance calcium-activated potassium (SK) channels are an
important group of potassium-selective ion channels. SK channels display
more pronounced expression in the atrium relative to the ventricle. Current
evidence relating to the functional role of SK channels in the atria is
conflicting and whether these channels contribute to atrial repolarization
under physiological circumstances is a matter of debate. Multiple studies
have, however, reported that SK channels are important mediators of
proarrhythmogenic electrical remodeling in the atria. In keeping with their
expression profile, SK channels do not appear to play a prominent role in
ventricular repolarization. SK channels represent potentially attractive
therapeutic targets for atrial fibrillation. A number of pharmacological
modulators of SK channels have been tested in animal models of atrial
fibrillation. However, these studies have also demonstrated inconsistent
results and have raised important questions regarding the proarrhythmogenic
potential of SK channel modulation. These findings have important
implications for drug development. This review summarizes the role of SK
channels in cardiac electrophysiology and discusses the potential role of
these channels as therapeutic targets.
Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All
rights reserved.
KEYWORDS:
Arrhythmia; Atrial fibrillation; Cardiac conduction; SK channels;
Ventricular fibrillation
PMID: 24681007 [PubMed - in process] | F****n
发帖数: 438 | 2 谢谢网友nimble，太热心了.
【在 F****n 的大作中提到】
: 那位大侠可以帮组查一下这几篇的全文吗？叩谢。
: 请发：y******[email protected].
: I.
: Role of small-conductance calcium-activated potassium channels in atrial
: electrophysiology and fibrillation in the dog.
: Qi XY1, Diness JG, Brundel BJ, Zhou XB, Naud P, Wu CT, Huang H, Harada M,
: Aflaki M, Dobrev D, Grunnet M, Nattel S.
: Author information
: Abstract
: BACKGROUND:
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