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Mechanosensitive Alterations of Action Potentials and Membrane Currents in Healthy and Diseased Cardiomyocytes: Cardiac Tissue and Isolated Cell

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Mechanosensitivity of the Heart

Part of the book series: Mechanosensitivity in Cells and Tissues ((MECT,volume 3))

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Abstract

Several electrophysiological alterations in the heart, which were ascribed to mechanoelectric feedback have been reported. First of all, they include changes in mechano-gated channels, mechanosensitive whole-cell currents which lead to membrane depolarization which is equivalent to a decrease in the resting membrane potential and elicited stretch-induced depolarizations, that appear during repolarization phase of cardiomyocyte action potential. Stretch-induced depolarization during action potentials provoke extra-action potentials when the stretch-induced depolarizations reach a threshold potential. Mechano-gated channels and mechanosensitive whole-cell currents are the cellular meachanisms underlying this phenomenon. In this review we discuss some open questions about mechanosensitive ionic currents in freshly isolated single cardiomyocytes. We will demonstrate certain methods of direct mechanical deformation of isolated cardiomyocytes for the purpose of electrophysiological investigation, including different experimental approaches to application of stretch and compression to pressure the cardiomyocytes. It is necessary to note that brick-like isolated cardiomyocytes stick to the bottom of the perfusion chamber in two different positions: edgewise, staying on the narrow side, or broad-wise. Partly these different positions of cells define the cell reaction to deformation. The reaction to stretch is identical in cardiomyocytes, occupying both positions (edgewise and broad-wise). However, the reaction to compression is different and is determined by the position of a cell. We demonstrate the possibility of simultaneous recording of mechano-gated single channels (in cell-attached mode) and mechanosensitive whole-cell currents during direct deformation of the whole cell. We discuss the results of stretch and compression of freshly isolated atrial cardiomyocytes from healthy and diseased animals and humans. Isolated cardiomyocytes respond to stretch with membrane depolarization, prolongation of their action potential (AP) and extra-APs that correlated with the amplitude of a non-selective stretch-activated current (ISAC). At negative potentials, ISAC is negative and carried by a transmembrane influx of Na+ ions. In this review we discuss some of the recent advances from intracellular recordings of the bioelectrical activity of cardiomyocytes during mechanical stretch of healthy and diseased tissues from animals and humans. The sensitivity of the AP to mechanical stretch was significantly increased in hypertrophied myocardium, and this could be related to the expression of SACs. We suppose that they are the basic findings that may explain mechanism of some arrhythmias and fibrillation.

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Authors and Affiliations

  1. Department of Fundamental and Applied Physiology, Russian State Medical University, Ostrovitjanova Str.1, 117997, Moscow, Russia

    Ilya Lozinsky

  2. Department of Fundamental and Applied Physiology, Russian State Medical University, Moscow, Russia

    Andre Kamkin

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  1. Ilya Lozinsky
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  2. Andre Kamkin
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  1. Dept. Fundamental &, Russian State Medical University, Ostrovitjanova Str. 1, Moskva, 117997, Russian Federation

    Andre Kamkin

  2. Dept. Fundamental &, Russian State Medical University, Ostrovitjanova Str. 1, Moskva, 117997, Russian Federation

    Irina Kiseleva

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Lozinsky, I., Kamkin, A. (2010). Mechanosensitive Alterations of Action Potentials and Membrane Currents in Healthy and Diseased Cardiomyocytes: Cardiac Tissue and Isolated Cell. In: Kamkin, A., Kiseleva, I. (eds) Mechanosensitivity of the Heart. Mechanosensitivity in Cells and Tissues, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2850-1_8

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