Redox control of cardiac rhythm

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.