Innovative techniques and new insights: studying cardiac ionic currents and action potentials in physiologically relevant conditions

Cardiac arrhythmias are associated with various forms of heart diseases. Ventricular arrhythmias present a significant risk for sudden cardiac death. Atrial fibrillations predispose to blood clots leading to stroke and heart attack. Scientists have been developing patch-clamp technology to study ion channels and action potentials (APs) underlying cardiac excitation and arrhythmias. Beyond the traditional patch-clamp techniques, innovative new techniques were developed for studying complex arrhythmia mechanisms. Here we review the recent development of methods including AP-Clamp, Dynamic Clamp, AP-Clamp Sequential Dissection, and Patch-Clamp-in-Gel. These methods provide powerful tools for researchers to decipher how the dynamic systems in excitation-Ca2+ signaling-contraction feedforward and feedback to control cardiac function and how their dysregulations lead to heart diseases.Las arritmias cardiacas están asociadas a diferentes tipos de enfermedad cardiaca. Las arritmias ventriculares constituyen un alto riesgo de muerte súbita. La fibrilación auricular predispone a coágulos sanguíneos que pueden producir accidentes cerebrovasculares e infarto miocárdico. Los científicos han desarrollado la técnica de patch-clamp para estudiar los canales iónicos y los potenciales de acción (PAs), que constituyen la base de la excitación y las arritmias cardiacas. Además de las clásicas técnicas de patch-clamp, se desarrollaron técnicas innovativas para estudiar los mecanismos complejos de las arritmias. En este trabajo, describimos diferentes métodos recientemente desarrollados tales como AP-clamp (“clampeo” del PA), Dynamic Clamp (“clampeo” dinámico), AP-Clamp Sequential Dissection, (disección secuencial del “clampeo” del AP), y Patch-Clamp-in-Gel (Patch clamp en gel). Estos métodos constituyen herramientas poderosas para descifrar cómo los sistemas dinámicos que constituyen la excitación-las señales de Ca2+ y la contracción, se retroalimentan para controlar la función cardiaca y cómo sus alteraciones llevan a la enfermedad cardiaca.Sociedad Argentina de Fisiologí

Spontaneous Calcium Release in Cardiac Myocytes: Store Overload and Electrical Dynamics

Heart disease is the leading cause of mortality in the United States. One cause of heart arrhythmia is calcium (Ca2+) mishandling in cardiac muscle cells. We adapt Izu\u27s et al. mathematical reaction-diffusion model of calcium in cardiac muscle cells, or cardiomyocytes implemented by Gobbert, and analyzed in Coulibaly et al. to include calcium being released from the sarcoplasmic reticulum (SR), the effects of buffers in the SR, particularly calsequestrin, and the effects of Ca2+ influx due to voltage across the cell membrane. Based on simulations of the model implemented in parallel using MPI, our findings aligned with known biological models and principles, giving us a thorough understanding of several factors that influence Ca2+ dynamics in cardiac myocytes. Specifically, dynamic calcium store will cap previous calcium blow-up seen in the model. Calcium channels located in spatial opposition of calcium release units produce more predictable intracellular calcium propagation. And we used multi-parametric calcium dynamics tables, which act as a multidimensional bifurcation diagram, to visualize parameter boundaries between different biophysical dynamics

Potassium currents in the heart: functional roles in repolarization, arrhythmia and therapeutics

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Complex electrophysiological remodeling in postinfarction ischemic heart failure

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