Article

Apico-basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium

Department of Physiology, University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary.
Cardiovascular Research (Impact Factor: 5.94). 04/2005; 65(4):851-60. DOI: 10.1016/j.cardiores.2004.11.022
Source: PubMed

ABSTRACT

The aim of the present study was to compare the apico-basal distribution of ion currents and the underlying ion channel proteins in canine and human ventricular myocardium.
Ion currents and action potentials were recorded in canine cardiomyocytes, isolated from both apical and basal regions of the heart, using whole-cell voltage clamp techniques. Density of channel proteins in canine and human ventricular myocardium was determined by Western blotting.
Action potential duration was shorter and the magnitude of phase-1 repolarization was significantly higher in apical than basal canine myocytes. No differences were observed in other parameters of the action potential or cell capacitance. Amplitude of the transient outward K(+) current (29.6+/-5.7 versus 16.5+/-4.4 pA/pF at +65 mV) and the slow component of the delayed rectifier K(+) current (5.61+/-0.43 versus 2.14+/-0.18 pA/pF at +50 mV) were significantly larger in apical than in basal myocytes. Densities of the inward rectifier K(+) current, rapid delayed rectifier K(+) current, and L-type Ca(2+) current were similar in myocytes of apical and basal origin. Apico-basal differences were found in the expression of only those channel proteins which are involved in mediation of the transient outward K(+) current and the slow delayed rectifier K(+) current: expression of Kv1.4, KChIP2, KvLQT1 and MinK was significantly higher in apical than in basal myocardium in both canine and human hearts.
The results suggest that marked apico-basal electrical inhomogeneity exists in the canine-and probably in the human-ventricular myocardium, which may result in increased dispersion, and therefore, cannot be ignored when interpreting ECG recordings, pathological alterations, or drug effects.

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    • "Using this concept we examined or re-examined the influence of some important experimental conditions like stimulation frequency, temperature, pH, redox-state and osmolarity on SV in canine ventricular myocytes. This preparation was chosen since it is believed to resemble most the human ventricular cells regarding their electrophysiological properties (Szabó et al. 2005; Szentandrássy et al. 2005), and because of the large mass of data on SV accumulated already in dogs. "
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    ABSTRACT: Beat-to-beat variability of action potential duration (short-term variability, SV) is an intrinsic property of mammalian myocardium. Since the majority of agents and interventions affecting SV may modify also action potential duration (APD), we propose here the concept of relative SV (RSV), where changes in SV are normalized to changes in APD and these data are compared to the control SV-APD relationship obtained by lengthening or shortening of action potentials by inward and outward current injections. Based on this concept the influence of the several experimental conditions like stimulation frequency, temperature, pH, redox-state and osmolarity were examined on RSV in canine ventricular myocytes using sharp microelectrodes. RSV was increased by high stimulation frequency (cycle lengths <0.7 s), high temperature (above 37ºC), oxidative agents (H2O2), while it was decreased by reductive environment. RSV was not affected by changes in pH (within the range of 6.4-8.4) and osmolarity of the solution (between 250-350 mOsm). The results indicate that changes in beat-to-beat variability of APD must be evaluated exclusively in terms of RSV; furthermore, some experimental conditions, including the stimulation frequency, redox-state and temperature have to be controlled strictly when analyzing alterations in the short-term variability of APD.
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    • "Apicobasal (AB): Apex-to-base dispersion of activationrecovery interval (ARI, a surrogate for APD) has been measured noninvasively in human as 42 ms [14] (mean of 7 subjects) with shorter ARI at the apex than the base. Experiments with canine and human tissue samples suggest the same [15]. We modelled this gradient by increasing g Ks by 50% of normal at the apex. "
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    Full-text · Conference Paper · Sep 2014
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    • "Kir2.2, and Kir2.3) ion channels (Karle et al. 2002; Marban 2002; Rook 2007). Earlier, the asymmetrical distribution and apico-basal inhomogeneity of Kir ion channels were investigated by Szabó et al. (2005) and Szentadrassy et al. (2005). They found that there are no transmural differences, at the protein level, in Kir2.1 channels in human and dog ventricles. "
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    ABSTRACT: Dilated cardiomyopathy (DCM) is a multifactorial disease characterized by left ventricular dilation that is associated with systolic dysfunction and increased action potential duration. The Kir2.x K(+) channels (encoded by KCNJ genes) regulate the inward rectifier current (IK1) contributing to the final repolarization in cardiac muscle. Here, we describe the transitions in the gene expression profiles of 4 KCNJ genes from healthy or dilated cardiomyopathic human hearts. In the healthy adult ventricles, KCNJ2, KCNJ12, and KCNJ4 (Kir2.1-2.3, respectively) genes were expressed at high levels, while expression of the KCNJ14 (Kir2.4) gene was low. In DCM ventricles, the levels of Kir2.1 and Kir2.3 were upregulated, but those of Kir2.2 channels were downregulated. Additionally, the expression of the DLG1 gene coding for the synapse-associated protein 97 (SAP97) anchoring molecule exhibited a 2-fold decline with increasing age in normal hearts, and it was robustly downregulated in young DCM patients. These adaptations could offer a new aspect for the explanation of the generally observed physiological and molecular alterations found in DCM.
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