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Redox control of cardiac rhythm

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Abstract

The rhythm of cardiac beats is generated by pacemaker cells differing from other cardiomyocytes by the presence of slow diastolic depolarization. Consistently activated transmembrane ionic currents provide cyclic excitation of pacemakers, forming the original “membrane clocks”. A new concept has been forwarded in the last decade according to which periodic fluctuations in myoplasmic Ca2+ level (“calcium clocks”) not only influence a course of “membrane clocks”, but they also can serve as independent generators of the rhythm. Transport of Ca2+ in cells is under constant influence of active forms of oxygen and nitrogen. Both superoxide and NO in moderate doses facilitate Ca2+ output from the sarcoplasmic reticulum, accelerating the course of “calcium clocks”, but in higher doses they have opposite effect that may be neutralized mainly by reduced glutathione. The control of cardiac rhythm by active forms of oxygen and nitrogen represents a feedback mechanism by which mitochondria and NO-synthases support Ca2+ homeostasis in cells that can be temporarily disturbed under mechanical loads or hypoxia.

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Abbreviations

ETC:

electron transport chain

GSNO:

S-nitrosoglutathione

GSNOR:

S-nitrosoglutathione reductase

NCX:

sarcolemmal Na+/Ca2+-exchange mechanism

NOS:

NO-synthase

ROS:

reactive oxygen species

RyR:

ryanodine receptor

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Authors and Affiliations

  1. Russian Cardiological Research and Production Complex, 3-ya Cherepkovskaya ul. 15a, 121552, Moscow, Russia

    V. I. Kapelko

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  1. V. I. Kapelko
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Correspondence to V. I. Kapelko.

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Published in Russian in Biokhimiya, 2012, Vol. 77, No. 11, pp. 1491–1503.

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Kapelko, V.I. Redox control of cardiac rhythm. Biochemistry Moscow 77, 1248–1257 (2012). https://doi.org/10.1134/S000629791211003X

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  • DOI: https://doi.org/10.1134/S000629791211003X

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