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Long-term in vitro recording of cardiac action potentials on microelectrode arrays for chronic cardiotoxicity assessment.

ABSTRACT: The reliable identification of chronic cardiotoxic effects in in vitro screenings is fundamental for filtering out toxic molecular entities before in vivo animal experimentation and clinical trials. Present techniques such as patch-clamp, voltage indicators, and standard microelectrode arrays do not offer at the same time high sensitivity for measuring transmembrane ion currents and low-invasiveness for monitoring cells over long time. Here, we show that optoporation applied to microelectrode arrays enables measuring action potentials from human-derived cardiac syncytia for more than 1 continuous month and provides reliable data on chronic cardiotoxic effects caused by known compounds such as pentamidine. The technique has high potential for detecting chronic cardiotoxicity in the early phases of drug development.

SUBMITTER: Iachetta G

PROVIDER: S-EPMC9859891 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Long-term in vitro recording of cardiac action potentials on microelectrode arrays for chronic cardiotoxicity assessment.

Iachetta Giuseppina G Melle Giovanni G Colistra Nicolò N Tantussi Francesco F De Angelis Francesco F Dipalo Michele M

Archives of toxicology 20230106 2

The reliable identification of chronic cardiotoxic effects in in vitro screenings is fundamental for filtering out toxic molecular entities before in vivo animal experimentation and clinical trials. Present techniques such as patch-clamp, voltage indicators, and standard microelectrode arrays do not offer at the same time high sensitivity for measuring transmembrane ion currents and low-invasiveness for monitoring cells over long time. Here, we show that optoporation applied to microelectrode ar ...[more]

PMID: 36607357

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Project description:Volcano-shaped microelectrodes (nanovolcanoes) functionalized with nanopatterned self-assembled monolayers have recently been demonstrated to report cardiomyocyte action potentials after gaining spontaneous intracellular access. These nanovolcanoes exhibit recording characteristics similar to those of state-of-the-art micro-nanoelectrode arrays that use electroporation as an insertion mechanism. In this study, we investigated whether the use of electroporation improves the performance of nanovolcano arrays in terms of action potential amplitudes, recording durations, and yield. Experiments with neonatal rat cardiomyocyte monolayers grown on nanovolcano arrays demonstrated that electroporation pulses with characteristics derived from analytical models increased the efficiency of nanovolcano recordings, as they enabled multiple on-demand registration of intracellular action potentials with amplitudes as high as 62 mV and parallel recordings in up to ~76% of the available channels. The performance of nanovolcanoes showed no dependence on the presence of functionalized nanopatterns, indicating that the tip geometry itself is instrumental for establishing a tight seal at the cell-electrode interface, which ultimately determines the quality of recordings. Importantly, the use of electroporation permitted the recording of attenuated cardiomyocyte action potentials during consecutive days at identical sites, indicating that nanovolcano recordings are nondestructive and permit long-term on-demand recordings from excitable cardiac tissues. Apart from demonstrating that less complex manufacturing processes can be used for next-generation nanovolcano arrays, the finding that the devices are suitable for performing on-demand recordings of electrical activity from multiple sites of excitable cardiac tissues over extended periods of time opens the possibility of using the devices not only in basic research but also in the context of comprehensive drug testing.

Project description:Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action potentials induced by drugs that target ion channels.

Dataset Information

Long-term in vitro recording of cardiac action potentials on microelectrode arrays for chronic cardiotoxicity assessment.

Publications

Long-term in vitro recording of cardiac action potentials on microelectrode arrays for chronic cardiotoxicity assessment.

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