Mitochondria in cardiomyocyte Ca2+ signaling

Abstract

Ca2+ signaling is of vital importance to cardiac cell function and plays an important role in heart failure. It is based on sarcolemmal, sarcoplasmic reticulum and mitochondrial Ca2+ cyclings. While the first two are well characterized, the latter remains unclear, controversial and technically challenging. In mammalian cardiac myocytes, Ca2+ influx through L-type calcium channels in the sarcolemmal membrane triggers Ca2+ release from the nearby junctional sarcoplasmic reticulum to produce Ca2+ sparks. When this triggering is synchronized by the cardiac action potential, a global [Ca2+]i transient arises from the coordinated Ca2+ release events. The ends of intermyofibrillar mitochondria are located within 20 nm of the junctional sarcoplasmic reticulum and thereby experience the high local [Ca2+] during the Ca2+ release process. Both local and global Ca2+ signals may thus influence calcium signaling in mitochondria and, reciprocally, mitochondria may contribute to local control of calcium signaling. In addition to the intermyofibrillar mitochondria, morphologically distinct mitochondria are also located in the perinuclear and subsarcolemmal regions of the cardiomyocyte and thus experience different local [Ca2+]. Here we review the literature in regard to several issues of broad interest: (1) the ultrastructural basis for mitochondrion - sarcoplasmic reticulum cross-signaling; (2) mechanisms of sarcoplasmic reticulum signaling; (3) mitochondrial calcium signaling; and (4) the possible interplay of calcium signaling between the sarcoplasmic reticulum and adjacent mitochondria. Finally, this review discusses experimental findings and mathematical models of cardiac calcium signaling between the sarcoplasmic reticulum and mitochondria, identifies weaknesses in these models, and suggests strategies and approaches for future investigations.

The role of mitochondria in cardiac development and protection

“…It has been suggested that IFM primarily supply ATP for the contractile system, whereas SSM provide the energy for the transport of electrolytes and metabolites across the sarcolemma [71]. IFM are also central for mitochondrial Ca 2+ cycling due to their proximity to the sarcoplasmic reticulum [72].…”

Mitochondrial functional specialization in glycolytic and oxidative muscle fibers: tailoring the organelle for optimal function

“…More specifically, in fast-glycolytic muscle, mitochondria are likely exposed to large increases in matrix [Ca 2ϩ ] compared with mitochondria from slow-oxidative muscle due to: 1) the large and rapid Ca 2ϩ surges that occur during contractions (21); 2) the physical proximity of mitochondria to large SR Ca 2ϩ stores (64,72,102); and 3) the small mitochondrial volume density and thus the low distribution volume for Ca 2ϩ in the matrix (12) (Fig. 3D).…”

“…3D). In fast-glycolytic fibers, a higher Ca 2ϩ threshold for PTP opening may ensure proper operation of the PTP in the flickering mode [which regulates ⌬⌿, ROS production and Ca 2ϩ signaling waves (17,28,64)], and prevention of accidental switch to the high-conductance mode involved in cell death signaling. Further work is, however, required to validate this hypothesis.…”

Non-invasive Video Image-based Analysis Method Coupled to Field Potential Recording for Evaluation of the Drug-induced Effect in Cardiac Tissue

“…This is expected since Ca 2+ release from the sarcoplasmic reticulum which underlies cardiac contraction in general is triggered and coordinated with the entry of Ca 2+ from the cytoplasm. 28 As Na + channel blocker, Quinidine affects the inward Na + flux and the fast depolarization phase of cardiac action potential which delays the activation of K + channels and Ca 2+ channels. Thus, it prolongs the cardiac potential and subsequently prolongs the beat interval.…”