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Front Physiol. 2018 Feb 13;9:61. doi: 10.3389/fphys.2018.00061. eCollection 2018.

Sub-cellular Electrical Heterogeneity Revealed by Loose Patch Recording Reflects Differential Localization of Sarcolemmal Ion Channels in Intact Rat Hearts.

Frontiers in physiology

Igor V Kubasov, Andrei Stepanov, Danila Bobkov, Przemysław B Radwanski, Maxim A Terpilowski, Maxim Dobretsov, Sandor Gyorke

Affiliations

  1. I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, Saint-Petersburg, Russia.
  2. Institute of Cytology RAS, Saint-Petersburg, Russia.
  3. Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, Ohio State University, Columbus, OH, United States.
  4. Division of Pharmacy Practice and Science, College of Pharmacy, Ohio State University, Columbus, OH, United States.
  5. Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.

PMID: 29487533 PMCID: PMC5816904 DOI: 10.3389/fphys.2018.00061

Abstract

The cardiac action potential (AP) is commonly recoded as an integral signal from isolated myocytes or ensembles of myocytes (with intracellular microelectrodes and extracellular macroelectrodes, respectively). These signals, however, do not provide a direct measure of activity of ion channels and transporters located in two major compartments of a cardiac myocyte: surface sarcolemma and the T-tubule system, which differentially contribute to impulse propagation and excitation-contraction (EC) coupling. In the present study we investigated electrical properties of myocytes within perfused intact rat heart employing loose patch recording with narrow-tip (2 μm diameter) extracellular electrodes. Using this approach, we demonstrated two distinct types of electric signals with distinct waveforms (single peak and multi-peak AP; AP1 and AP2, respectively) during intrinsic pacemaker activity. These two types of waveforms depend on the position of the electrode tip on the myocyte surface. Such heterogeneity of electrical signals was lost when electrodes of larger pipette diameter were used (5 or 10 μm), which indicates that the electric signal was assessed from a region of <5 μm. Importantly, both pharmacological and mathematical simulation based on transverse (T)-tubular distribution suggested that while the AP1 and the initial peak of AP2 are predominantly attributable to the fast, inward Na

Keywords: T-tubule; action potential; cardiac muscle; excitation-contraction coupling; ion channels and transporters

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