Comparison between intracellular and extracellular direct current recordings of sinus node activity for evaluation of sinoatrial conduction time.

Haberl, Ralph; Steinbeck, Gerhard; Lüderitz, Berndt

doi:10.1161/01.cir.70.4.760

Cited by 18 publications

(8 citation statements)

References 17 publications

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“…This was also demonstrated in a recent report by the characterization of intrinsic action potential (AP) parameters during simultaneous recording of APs and FPs in native murine embryonic cardiomyocytes. As has been described for other models [26][27][28], not only different AP and FP morphologies representing atrial, ventricular or pacemaker-like potentials [29,30], but also a linear relationship between AP and FP rise time as well as a linear relationship between AP duration and FP duration was demonstrated [16]. In line with these similarities between APs and FPs, it was shown that individual ion channels, i.e.…”

Section: Discussionsupporting

confidence: 71%

Beta-adrenergic and Muscarinic Modulation of Human Embryonic Stem Cell-derived Cardio-myocytes

Reppel

Boettinger

Hescheler

2004

Cell Physiol Biochem

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Background: Embryonic stem cells provide the most promising tool for cell replacement therapy including transplantation of human embryonic stem (hES) cell- derived cardiomyocytes in the infarcted area of the heart. Here we provide data for differentiation of cardiomyocytes from hES cells and firstly describe their hormonal modulation. Methods: Using Micro-Electrode Arrays as a novel electrical mapping technique of beating cardiomyocyte clusters within whole hES cell aggregates, we were able to measure the field potential generation and morphology changes during hormonal modulation. Results: We found that isoproterenol provokes, similar to the mouse ES cell system, a strong positive chronotropic effect with an EC₅₀ of around 10^-8 M. Moreover, isoproterenol stimulated with a higher EC₅₀ value the slow field potential amplitude, FP_slow, indicating a stimulation of Ca²⁺ channels in ventricular-like ES cell-derived cardiomyocytes which is shown to be clearly independent from frequence modulation. In contrast, carbachol (10 µM) produced a transient negative chronotropic effect but had no effect on FP_slow. Conclusion: The Micro-Electrode system allows measurement of ionic channel modulation and chronotropic responsiveness in a pharmacological screening setup. Moreover, all our data indicate that cardiomyocytes derived from human embryonic stem cells exhibit a physiological response to the major hormones of the vegetative nervous system and might therefore serve as an ideal candidate for the use in cell replacement strategies.

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Section: Discussionsupporting

confidence: 71%

Beta-adrenergic and Muscarinic Modulation of Human Embryonic Stem Cell-derived Cardio-myocytes

Reppel

Boettinger

Hescheler

2004

Cell Physiol Biochem

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“…Although recordings of extracellular FPs have a long history in cardiac electrophysiology, the interpretation of these signals was mostly limited to the analysis of the beating frequency and the direction of excitation spread [14,20,34,35]. In the present study we demonstrated that the FPs recorded from multicellular preparations of isolated mouse cardiomyocytes contain information about the AP rise time, the AP duration and individual transmembrane currents of the cells covering the electrodes.…”

Section: Discussionmentioning

confidence: 55%

“…The lack of FP pre in these FPs, which was reported to represent surrounding previously excited tissue [23], supports this hypothesis. Correspondingly, slowly declining FPs in isolated rabbit sinus node were previously interpreted to represent the origin of excitation [34,35,39]. In these reports, the lack of FP pre and the slow decline of the FP were used as qualitative indicators of the pacemaker region.…”

Section: Rise Time Of Ap and Fpmentioning

confidence: 99%

Estimation of Action Potential Changes from Field Potential Recordings in Multicellular Mouse Cardiac Myocyte Cultures

Halbach

Egert²,

Hescheler³

et al. 2003

Cell Physiol Biochem

189

174

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Background: Extracellular recordings of electrical activity with substrate-integrated microelectrode arrays (MEAs) enable non-invasive long-term monitoring of contracting multicellular cardiac preparations. However, to characterize not only the spread of excitation and the conduction velocity from field potential (FP) recordings, a more rigorous analysis of FPs is necessary. Therefore in this study we aim to characterize intrinsic action potential (AP) parameters by simultaneous recording of APs and FPs. Methods: A MEA consisting of 60 substrate-integrated electrodes is used to record the FP-waveform from multicellular preparations of isolated embryonic mouse cardiomyocytes. Simultaneous current clamp recordings in the vicinity of individual microelectrodes and pharmacological interventions allowed us to correlate FP and AP components and their time course. Results: The experiments revealed a linear relationship between AP rise time and FP rise time as well as a linear relationship between AP duration and FP duration. Furthermore a direct contribution of the voltage dependent Na⁺- and Ca²⁺-current to the FP could be identified. Conclusion: The characterization of the FP allows us for the first time to estimate AP changes and the contribution of individual current components to the AP by the help of non-invasive recording within a multicellular cardiac preparation during long-term culture.

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“…As a result, conduction velocity is lowest (0.03-0.05 m/s) in the central region and increases to 1 m/s at the periphery. The changes in cellto-cell contacts are thought to contribute to the pacemaker activity of the sinoatrial node and to its capability of driving the myocardial function [21][22][23][24][25].…”

Section: Reviews a View Of The Cardiac Rhythm Control: Intrinsic Regumentioning

confidence: 99%

“…Thus, pacemaker shifts in the sinoatrial node can be considered in terms of doubling: when the pacemaker activity is inhibited in the usual dominant pacemaker site, its function is taken over by another region of the node [21]. As a consequence, the HR changes.…”

Section: Reviews a View Of The Cardiac Rhythm Control: Intrinsic Regumentioning

confidence: 99%

A view of the cardiac rhythm control: Intrinsic regulation

Nozdrachev

Kotel'nikov²,

Mazhara³

et al. 2005

Hum Physiol

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by Nozdrachev, Kotel'nikov, Mazhara, Naumov. † Mechanisms regulating the heart rate (HR) continue to be the focus of various studies, which is due to the development of new noninvasive methods for assessing the state of the autonomic nervous system. One such method is spectral analysis of HR variability. It should be noted that the mechanisms responsible for oscillatory modulation of the cardiac rhythm and, consequently, for its spectrum are still obscure to a great extent. To gain a better understanding of them, it is necessary to elucidate the mechanisms controlling the HR. The HR control involves the mechanisms regulating the blood pressure, cardiac output, and total peripheral resistance. However, these issues have been considered in numerous original papers and reviews and are beyond the scope of this work.It is commonly accepted that the HR is determined by the rhythmic activity of pacemaker cells of the sinoatrial node. These cells are capable of spontaneous diastolic depolarization of the membrane potential. Comprehension of the mechanisms of diastolic depolarization is of immense importance for a better understanding of the neural and humoral regulation of the HR.Quantitative studies of ionic currents in pacemaker cells and mathematical models based on their results † Deceased. made it possible to assume the following scenario for rhythm generation [1,2].It is known that the algebraic sum of inward and outward ionic currents across the cell membrane is zero at physiological rest. This is the condition for constancy of the resting potential. Inward currents are carried mostly by sodium ions and, to a lesser extent, by calcium ions. Outward currents are due to potassium ions. A change in their balance to a prevalence of inward currents over outward currents leads to depolarization and, consequently, allows autorhythmic activity. At least two conditions are necessary for this activity to be sustained: (1) at the resting potential, the net inward current exceeds the net outward current by a value sufficient for initiating regenerative depolarization, and (2) at the action potential, the outward current increases to a level sufficient for membrane repolarization such that it abolishes the inactivation of channels carrying the inward current and inactivates channels carrying the outward current. Condition (1) can be accomplished either by primarily increasing the inward (fast or slow) current or by primarily decreasing the outward current. A combination of such changes is also possible. Pacemaker cells employ both of these mechanisms (see below).A specific feature of pacemaker cells of the sinoatrial node is a higher constant background sodium REVIEWS Abstract -Regulation of the cardiac rhythm is intricate and occurs at least at two major levels, intrinsic and extrinsic. In turn, each of these levels can be divided into several sublevels. The factors regulating the cardiac activity eventually affect the duration of spontaneous diastolic depolarization of pacemaker myocytes of the sinoatrial node and, to a ...

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Comparison between intracellular and extracellular direct current recordings of sinus node activity for evaluation of sinoatrial conduction time.

Cited by 18 publications

References 17 publications

Beta-adrenergic and Muscarinic Modulation of Human Embryonic Stem Cell-derived Cardio-myocytes

Beta-adrenergic and Muscarinic Modulation of Human Embryonic Stem Cell-derived Cardio-myocytes

Estimation of Action Potential Changes from Field Potential Recordings in Multicellular Mouse Cardiac Myocyte Cultures

A view of the cardiac rhythm control: Intrinsic regulation

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