The response of Ca-mediated action potentials and contractile activity in mammalian ventricular myocardium towards alkalosis

Kohlhardt, M.; Haap, K.

doi:10.1007/bf01937735

Cited by 4 publications

(2 citation statements)

References 6 publications

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“…All the data shown earlier were collected using a commercially available amplifier (MEA 1060, MCS), which requires that the culture be taken out of the incubator and placed on the recording stage for electrophysiology measurements. The health and the electrophysiological properties of cardiomyocytes are sensitive to experimental conditions such as temperature, humidity, and CO 2 level 47 , 48 . To reduce environmental variabilities, we recently collaborated with Cyion Technologies to design a miniaturized recording stage for in situ long term recording inside a CO 2 incubator, which is controlled through a cable connected to a computer outside the incubator.…”

Section: Resultsmentioning

confidence: 99%

Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes

et al. 2022

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Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. However, the large variability in success rate and signal strength have hindered nanoelectrodes from being broadly adopted for proarrhythmia drug assessment. In this work, we develop vertically-aligned nanocrown electrodes that are mechanically robust and achieve > 99% success rates in obtaining intracellular access through electroporation. We validate the accuracy of nanocrown electrode recordings by simultaneous patch clamp recording from the same cell. Finally, we demonstrate that nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four incremental drug doses. Our technology development provides an advancement towards establishing an iAP screening assay for preclinical evaluation of drug-induced arrhythmogenicity.

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Section: Resultsmentioning

confidence: 99%

Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes

et al. 2022

View full text Add to dashboard Cite

Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. However, the large variability in success rate and signal strength have hindered nanoelectrodes from being broadly adopted for proarrhythmia drug assessment. In this work, we develop vertically-aligned nanocrown electrodes that are mechanically robust and achieve > 99% success rates in obtaining intracellular access through electroporation. We validate the accuracy of nanocrown electrode recordings by simultaneous patch clamp recording from the same cell. Finally, we demonstrate that nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four incremental drug doses. Our technology development provides an advancement towards establishing an iAP screening assay for preclinical evaluation of drug-induced arrhythmogenicity.

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“…In-situ recording using miniaturized Petri-dish-like recording stage All the data shown earlier were collected using a commercially available amplifier (MEA 1060, MCS), which requires that the culture be taken out of the incubator and placed on the recording stage for electrophysiology measurements. The health and the electrophysiological properties of cardiomyocytes are sensitive to experimental conditions such as temperature, humidity, and CO2 level (Kohlhardt and Haap 1976;Cedrini and Alloatti 1979). To reduce environmental variabilities, we recently collaborated with Cyion Technologies to design a miniaturized recording stage for in situ long term recording inside a CO2 incubator, which is controlled through a cable connected to a computer outside the incubator.…”

Section: Nea Enables Self-referencing Assessment Of Drug-induced Changes Of Iapsmentioning

confidence: 99%

Nanocrown electrodes for reliable and robust intracellular recording of cardiomyocytes and cardiotoxicity screening

Jahed

Yong

Tsai

et al. 2021

Preprint

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Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. However, the conventional patch clamp techniques for measuring iAPs are either laborious and low throughput or not suitable for measuring electrically connected cardiomyocytes. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. Nanoelectrodes show great promise, but the large variability in success rate, signal strength, and the low throughput of device fabrication have hindered them from being broadly adopted for proarrhythmia drug assessment. In this work, we developed vertically-aligned and semi-hollow nanocrown electrodes that are mechanically robust and made through a scalable fabrication process. Nanocrown electrodes achieve >99% success rates in obtaining intracellular access through electroporation, allowing reliable recordings of iAPs from human pluripotent stem-cell-derived cardiomyocytes (hPSC-CMs). The accuracy of nanocrown electrode recordings is validated by simultaneous patch clamp recording from the same cell. Nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four to five incremental drug doses. In this way, the dose-response data is self-referencing, which avoids the cell-to-cell variations inherent to hPSC-CMs. We are hopeful that this technology development is a step towards establishing an iAP screening assay for preclinical evaluation of drug-induced arrhythmogenicity.

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Calcium and Other Divalent Cations as Charge Carriers of the Slow Inward Current in Heart Muscle

Kohlhardt

1981

Handbook of Stable Strontium

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The response of Ca-mediated action potentials and contractile activity in mammalian ventricular myocardium towards alkalosis

Cited by 4 publications

References 6 publications

Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes

Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes

Nanocrown electrodes for reliable and robust intracellular recording of cardiomyocytes and cardiotoxicity screening

Calcium and Other Divalent Cations as Charge Carriers of the Slow Inward Current in Heart Muscle

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