Abstract
In rabbit atrial myocytes Ca signaling has unique features due to the lack of transverse (t) tubules, the spatial arrangement of mitochondria and the contribution of inositol-1,4,5-trisphosphate (IP3) receptor-induced Ca release (IICR). During excitation-contraction coupling action potential-induced elevation of cytosolic [Ca] originates in the cell periphery from Ca released from the junctional sarcoplasmic reticulum (j-SR) and then propagates by Ca-induced Ca release from non-junctional (nj-) SR toward the cell center. The subsarcolemmal region between j-SR and the first array of nj-SR Ca release sites is devoid of mitochondria which results in a rapid propagation of activation through this domain, whereas the subsequent propagation through the nj-SR network occurs at a velocity typical for a propagating Ca wave. Inhibition of mitochondrial Ca uptake with the Ca uniporter blocker Ru360 accelerates propagation and increases the amplitude of Ca transients (CaTs) originating from nj-SR. Elevation of cytosolic IP3 levels by rapid photolysis of caged IP3 has profound effects on the magnitude of subcellular CaTs with increased Ca release from nj-SR and enhanced CaTs in the nuclear compartment. IP3 uncaging restricted to the nucleus elicites ‘mini’-Ca waves that remain confined to this compartment. Elementary IICR events (Ca puffs) preferentially originate in the nucleus in close physical association with membrane structures of the nuclear envelope and the nucleoplasmic reticulum. The data suggest that in atrial myocytes the nucleus is an autonomous Ca signaling domain where Ca dynamics are primarily governed by IICR.
Highlights
In atrial myocytes the mechanism of excitation-contraction coupling (ECC) and action potential (AP) induced Ca release from the sarcoplasmic reticulum (SR) reveals unique features that are strikingly different from ventricular myocytes
1) We investigated in details how the spatial organization of mitochondria affects the centripetal propagation of Ca release during ECC. 2) We present unique features of nuclear IP3R-induced Ca release (IICR) in atrial myocytes that support the hypothesis of autonomous Ca signaling in the nuclear domain
Membrane staining with the fluorescent probe WGA-Alexa 594 revealed a regular dense t-tubular network in rabbit ventricular cells (Fig. 1A, a), whereas in atrial myocytes membrane staining was limited to the cell periphery consistent with the absence of t-tubules (Fig. 1B, a)
Summary
In atrial myocytes the mechanism of excitation-contraction coupling (ECC) and action potential (AP) induced Ca release from the sarcoplasmic reticulum (SR) reveals unique features that are strikingly different from ventricular myocytes.
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