Asymmetrical distribution of ion channels in canine and human left-ventricular wall: epicardium versus midmyocardium
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The aim of the present study was to compare the distribution of ion currents and the major underlying ion channel proteins in canine and human subepicardial (EPI) and midmyocardial (MID) left-ventricular muscle. Ion currents and action potentials were recorded from canine cardiomyocytes derived from the very superficial EPI and central MID regions of the left ventricle. Amplitude, duration and the maximum velocity of depolarization of the action potential were significantly greater in MID than EPI myocytes, whereas phase-1 repolarization was more pronounced in the EPI cells. Amplitudes of the transient outwards K+ current (29.5+/-1.5 vs. 19.0+/-2.3 pA/pF at +50 mV) and the slow component of the delayed rectifier K+ current (10.3+/-2.3 vs. 6.5+/-1.0 pA/pF at +50 mV) were significantly larger in EPI than in MID myocytes under whole-cell voltage-clamp conditions. The densities of the inwards rectifier K+ current, rapid delayed rectifier K+ current and L-type Ca2+ current were similar in both cell types. Expression of channel proteins in both canine and human ventricular myocardium was determined by Western blotting. In the canine heart, the expression of Kv4.3, Kv1.4, KChIP2 and KvLQT1 was significantly higher, and that of Nav1.5 and MinK much lower, in EPI than in MID. No significant EPI-MID differences were observed in the expression of the other channel proteins studied (Kir2.1, alpha1C, HERG and MiRP1). Similar results were obtained in human hearts, although the HERG was more abundant in the EPI than in the MID layer. In the canine heart, the EPI-MID differences in ion current densities were proportional to differences in channel protein expression. Except for the density of HERG, the pattern of EPI-MID distribution of ion-channel proteins was identical in canine and human ventricles.
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Expression patterns of various ion channels, both apico-basally and transmurally, are very similar between canine and human with some exceptions.
“expression patterns of various ion channels both apico-basally (Szentadrassy, et al., 2005) and transmurally (Szabo, et al., 2005; Zicha, et al., 2004) with some exceptions, are very similar between these two species.”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Szabo, et al., 2005
Despite high similarity between human and canine myocardium, some differences have been reported, including resting and exercise heart rates, kinetics of Ito current inactivation, its recovery, molecular size of corresponding ion channels, sensitivity to flecanide, and transmural epicardial:endocardial expression levels of HERG ion channel.
“Such differences include resting and exercise heart rates (see above), kinetics of Ito current inactivation, its recovery, and molecular size of its corresponding ion channels, sensitivity to flecanide (Akar, et al., 2004), and transmural epicardial:endocardial expression levels of HERG ion channel (Szabo, et al., 2005).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Szabo, et al., 2005
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- Authors
- Szabó, G., Szentandrássy, N., Bíró, T., Tóth, B. I., Czifra, G., Magyar, J., Bányász, T., Varró, A., Kovács, L., & Nánási, P. P.
- Affiliations
- University of Debrecen (HU)
- Corresponding author
- Nánási, Péter P.
- ORCID
- Venue
- Pflügers Archiv - European Journal of Physiology
- Published
- 2005-06-11
- Volume
- 450
- Issue
- 5
- Pages
- 307-316
- ISSN
- 0031-6768 (ISSN-L)
- 1432-2013
- OpenAlex
- W2093186412
- Cited by
- 134
- References
- 32
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 11 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 16 · 2016: 5 · 2015: 6 · 2014: 8 · 2013: 8 · 2012: 9
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Pflügers Archiv - European Journal of Physiology (publishedVersion)
- PubMed (publishedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Keywords
- ion channel distribution, left ventricle, subepicardium, action potential, transient outward potassium current, delayed rectifier potassium current, L-type calcium current, inward rectifier potassium current, hERG, Kv4.3, Kv1.4, KCNQ1, cardiac sodium channel, mink, ventricular repolarization
- MeSH terms
- Action Potentials, Animals, Dogs, Female, Humans, Ion Channels, Male, Membrane Potentials, Pericardium, Blotting, Western, Ventricular Function, Calcium Channels, L-Type, Myocytes, Cardiac, Ether-A-Go-Go Potassium Channels
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