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

  • Karin P. Hammer
  • Lars S. Maier
Chapter
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol.)

Abstract

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.

Keywords

Calcium signaling Alternans Calcium release SR leak ECC Cardiac myocyte 

Abbreviations

[Ca2+]

Ca2+ concentration

[Ca2+]cleft

Ca2+ concentration in the cleft

[Ca2+]i

Intracellular Ca2+ concentration

[Ca2+]mito

Mitochondrial Ca2+ concentration

[Ca2+]SR

SR-Ca2+ concentration

AP

Action potential

BCL

Basic cycle length

CaMKII

Ca2+/calmodulin-dependent protein kinase II

CaT

Ca2+ transient

CICR

Ca2+-induced Ca2+ release

DI

Diastolic interval

ECC

Excitation-contraction coupling

ETC

Excitation transcription coupling

GPCR

G-protein-coupled receptor

GPI

Glycophosphatidylinositol

ICa

Ca2+ current

INCX

NCX current

InsP3R

Inositol triphosphate receptor

LTCC

L-type Ca2+ channel

MCU

Mitochondrial Ca2+ uniporter

MTPT

Mitochondrial permeability transition pore

NCX

Na+-Ca2+ exchanger

PKA

Protein kinase A

RyR

Ryanodine receptor

SERCA

Sarco-endoplasmatic reticulum ATPase

SR

Sarcoplasmatic reticulum

TRP

Transient receptor potential

t-tubules

Transverse tubules

Notes

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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