The Role of Local Ca2+ Release for Ca2+ Alternans and SR-Ca2+ Leak

  • Karin P. HammerEmail author
  • Lars S. MaierEmail author
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol., volume 3)


Cardiac Ca2+ is the second messenger transducing electrical signals into mechanical responses during excitation-contraction coupling (ECC). The unique morphology of ventricular myocytes plays a pivotal role during ECC and assures the synchronous Ca2+ release into the cytosol and the orchestrated interplay of the channels and modulators involved. Alterations of one or more of the key players will cause instabilities during Ca2+ cycling that can have detrimental effects on the function of the myocyte. Local Ca2+ release is the underlying mechanism during ECC, and single spontaneous release events occur rarely under healthy conditions but increase during disease progression. This shift in the fine-tuned release machinery can propel toward more severe arrhythmogenic behavior. Increased SR leak can set the basis for Ca2+ alternans in single myocytes among other factors. Alternans as arrhythmogenic factors mechanistically link cardiac mechanical dysfunction and sudden cardiac death. On a cellular level, alternans can be seen early on during disease progression. Here we want to highlight the role of localized Ca2+ release for the development and maintenance of alternans in single myocytes and the intact heart.


Calcium signaling Alternans Calcium release SR leak ECC Cardiac myocyte 



Ca2+ concentration


Ca2+ concentration in the cleft


Intracellular Ca2+ concentration


Mitochondrial Ca2+ concentration


SR-Ca2+ concentration


Action potential


Basic cycle length


Ca2+/calmodulin-dependent protein kinase II


Ca2+ transient


Ca2+-induced Ca2+ release


Diastolic interval


Excitation-contraction coupling


Excitation transcription coupling


G-protein-coupled receptor




Ca2+ current


NCX current


Inositol triphosphate receptor


L-type Ca2+ channel


Mitochondrial Ca2+ uniporter


Mitochondrial permeability transition pore


Na+-Ca2+ exchanger


Protein kinase A


Ryanodine receptor


Sarco-endoplasmatic reticulum ATPase


Sarcoplasmatic reticulum


Transient receptor potential


Transverse tubules


Compliance with Ethical Standards

Conflict of Interest Statement

K. P. Hammer has no conflict of interest. L. S. Maier receives funding from Gilead and Sanofi.


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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.University Hospital Regensburg, Internal Medicine II, CardiologyRegensburgGermany

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