Optical recording of calcium currents during impulse conduction in cardiac tissue

Jousset, Florian; Rohr, Stephan

doi:10.1117/1.nph.2.2.021011

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…Therefore, as in previous work (Prudat and Kucera, 2014), we increased the maximal conductance of I CaL from 0.09 to 0.18 mS/μF and accelerated its gating kinetics [rate constants of the activation gate d multiplied by 30, rate constants of the inactivation gate f multiplied by 2, Equations (2–5)]. The adjusted I CaL exhibited a time to peak of ~1 ms, comparable to previous experimental and modeling studies (Shaw and Rudy, 1997; Linz and Meyer, 2000; Wang and Sobie, 2008; Prudat and Kucera, 2014; Jousset and Rohr, 2015). We note that the role of I CaL in sustaining propagation during a reduction of coupling becomes important only when intercellular coupling is decreased by >90% (Shaw and Rudy, 1997).…”

Section: Methodssupporting

confidence: 83%

Myofibroblasts Electrotonically Coupled to Cardiomyocytes Alter Conduction: Insights at the Cellular Level from a Detailed In silico Tissue Structure Model

et al. 2016

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Fibrotic myocardial remodeling is typically accompanied by the appearance of myofibroblasts (MFBs). In vitro, MFBs were shown to slow conduction and precipitate ectopic activity following gap junctional coupling to cardiomyocytes (CMCs). To gain further mechanistic insights into this arrhythmogenic MFB-CMC crosstalk, we performed numerical simulations in cell-based high-resolution two-dimensional tissue models that replicated experimental conditions. Cell dimensions were determined using confocal microscopy of single and co-cultured neonatal rat ventricular CMCs and MFBs. Conduction was investigated as a function of MFB density in three distinct cellular tissue architectures: CMC strands with endogenous MFBs, CMC strands with coating MFBs of two different sizes, and CMC strands with MFB inserts. Simulations were performed to identify individual contributions of heterocellular gap junctional coupling and of the specific electrical phenotype of MFBs. With increasing MFB density, both endogenous and coating MFBs slowed conduction. At MFB densities of 5–30%, conduction slowing was most pronounced in strands with endogenous MFBs due to the MFB-dependent increase in axial resistance. At MFB densities >40%, very slow conduction and spontaneous activity was primarily due to MFB-induced CMC depolarization. Coating MFBs caused non-uniformities of resting membrane potential, which were more prominent with large than with small MFBs. In simulations of MFB inserts connecting two CMC strands, conduction delays increased with increasing insert lengths and block appeared for inserts >1.2 mm. Thus, electrophysiological properties of engineered CMC-MFB co-cultures depend on MFB density, MFB size and their specific positioning in respect to CMCs. These factors may influence conduction characteristics in the heterocellular myocardium.

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Section: Methodssupporting

confidence: 83%

Myofibroblasts Electrotonically Coupled to Cardiomyocytes Alter Conduction: Insights at the Cellular Level from a Detailed In silico Tissue Structure Model

et al. 2016

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“…Besides being suited to validate optogenetic sensors and actuators with respect to co-localized electrical measurements, the POEMS system likely permits the recording of signals from optical reporters different from GEVIs like genetically engineered calcium indicators 37 and can be used in conjunction with optogenetic actuators controlling, e.g., cell signaling 38 . Further conceivable applications include investigations of the dependence of arrhythmogenic slow conduction on optically measured Ca 2+ inward currents 39 and the elucidation of consequences of heterocellular electrotonic crosstalk between cardiomyocytes and noncardiomyocytes for cardiac activation and the precipitation of cardiac arrhythmias. Finally, the conceptual approach offers future flexibility because an increase of the spatial resolution, the inclusion of additional types of sensors, and the adaptation to larger hearts can be readily accomplished by redesigning the 3D-printed heart container only while keeping all other system components unchanged.…”

Section: Discussionmentioning

confidence: 99%

Enabling comprehensive optogenetic studies of mouse hearts by simultaneous opto-electrical panoramic mapping and stimulation

et al. 2021

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During the last decade, cardiac optogenetics has turned into an essential tool for investigating cardiac function in general and for assessing functional interactions between different myocardial cell types in particular. To advance exploitation of the unique research opportunities offered by this method, we develop a panoramic opto-electrical measurement and stimulation (POEMS) system for mouse hearts. The core of the experimental platform is composed of 294 optical fibers and 64 electrodes that form a cup which embraces the entire ventricular surface of mouse hearts and enables straightforward ‘drop&go’ experimentation. The flexible assignment of fibers and electrodes to recording or stimulation tasks permits a precise tailoring of experiments to the specific requirements of individual optogenetic constructs thereby avoiding spectral congestion. Validation experiments with hearts from transgenic animals expressing the optogenetic voltage reporters ASAP1 and ArcLight-Q239 demonstrate concordance of simultaneously recorded panoramic optical and electrical activation maps. The feasibility of single fiber optical stimulation is proven with hearts expressing the optogenetic voltage actuator ReaChR. Adaptation of the POEMS system to larger hearts and incorporation of additional sensors can be achieved by redesigning the system-core accordingly.

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Coupling between cardiac cells—An important determinant of electrical impulse propagation and arrhythmogenesis

Kléber

Jin

2021

Biophysics Reviews

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Cardiac arrhythmias are an important cause of sudden cardiac death—a devastating manifestation of many underlying causes, such as heart failure and ischemic heart disease leading to ventricular tachyarrhythmias and ventricular fibrillation, and atrial fibrillation causing cerebral embolism. Cardiac electrical propagation is a main factor in the initiation and maintenance of cardiac arrhythmias. In the heart, gap junctions are the basic unit at the cellular level that host intercellular low-resistance channels for the diffusion of ions and small regulatory molecules. The dual voltage clamp technique enabled the direct measurement of electrical conductance between cells and recording of single gap junction channel openings. The rapid turnover of gap junction channels at the intercalated disk implicates a highly dynamic process of trafficking and internalization of gap junction connexons. Recently, non-canonical roles of gap junction proteins have been discovered in mitochondria function, cytoskeletal organization, trafficking, and cardiac rescue. At the tissue level, we explain the concepts of linear propagation and safety factor based on the model of linear cellular structure. Working myocardium is adequately represented as a discontinuous cellular network characterized by cellular anisotropy and connective tissue heterogeneity. Electrical propagation in discontinuous cellular networks reflects an interplay of three main factors: cell-to-cell electrical coupling, flow of electrical charge through the ion channels, and the microscopic tissue structure. This review provides a state-of-the-art update of the cardiac gap junction channels and their role in cardiac electrical impulse propagation and highlights a combined approach of genetics, cell biology, and physics in modern cardiac electrophysiology.

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Optical recording of calcium currents during impulse conduction in cardiac tissue

Cited by 3 publications

References 29 publications

Myofibroblasts Electrotonically Coupled to Cardiomyocytes Alter Conduction: Insights at the Cellular Level from a Detailed In silico Tissue Structure Model

Myofibroblasts Electrotonically Coupled to Cardiomyocytes Alter Conduction: Insights at the Cellular Level from a Detailed In silico Tissue Structure Model

Enabling comprehensive optogenetic studies of mouse hearts by simultaneous opto-electrical panoramic mapping and stimulation

Coupling between cardiac cells—An important determinant of electrical impulse propagation and arrhythmogenesis

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