Spatiotemporal Visualization of Intracellular Ca2+ in Living Heart Muscle Cells Viewed by Confocal Laser Scanning Microscopy.

Tanaka, Hideo; Takamatsu, Tetsuro

doi:10.1267/ahc.36.193

Cited by 8 publications

(11 citation statements)

References 70 publications

(64 reference statements)

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“…By using our unique in situ rapid‐scanning confocal microscopy, we found that during consecutive heartbeats, individual myocytes exhibit spatiotemporally uniform Ca 2+ transients on excitation, while there is no remarkable [Ca 2+ ] i elevation during diastole (Fig. S1B) . In contrast, myocytes under [Ca 2+ ] i overload, caused by, e.g., membrane damage, exhibit spontaneous wave‐like elevations of local [Ca 2+ ] i that propagate within the individual myocytes, called Ca 2+ waves (Fig.…”

Section: Arrhthomogenesis Revealed By Functional Imaging Of Non‐electmentioning

confidence: 98%

“…6,15 In contrast, myocytes under [Ca 2þ ] i overload, caused by, e.g., membrane damage, exhibit spontaneous wave-like elevations of local [Ca 2þ ] i that propagate within the individual myocytes, called Ca 2þ waves ( Fig. S2A), 6,7,15 wellestablished Ca 2þ release events from the SR ( Fig. S2B & C).…”

Section: Roles Of Intracellular Ca 2þ Waves In Triggered Arrhythmiasmentioning

confidence: 99%

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Towards an integrated understanding of cardiac arrhythmogenesis − Growing roles of experimental pathology

Tanaka

Matsuyama

Takamatsu

2016

Pathology International

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Cardiac arrhythmias have long been regarded as derangement of electrical impulse initiation and conduction within the heart. However, underlying mechanisms for arrhythmogenesis are not fully understood solely from the electrophysiological viewpoint. This review article discusses pathogenesis of arrhythmias from non-electrical aspects, which were elucidated by spatiotemporal imaging of functional molecules in combination with morphological analysis of living heart tissues. Intracellular Ca ([Ca ] ) overload, caused by myocardial injury, provokes Ca waves that could lead to abnormal excitations, i.e., triggered arrhythmias. Depressed Ca release from the sarcoplasmic reticulum, caused by ischemia, heart failure, or T-tubular remodeling, results in spatiotemporally inhomogeneous [Ca ] dynamics that could disturb impulse conduction, leading to reentrant tachyarrhythmias. Impairment of the gap junction-mediated intercellular communications, which provokes derangement of impulse propagation of the myocardium, also leads to reentrant arrhythmias. Interpositions of non-cardiomyocytes, especially fibroblasts, in the myocardium could also contribute to arrhythmogenesis via heterocellular gap-junctional coupling with cardiomyocytes. Furthermore, alterations in myocardial histology, e.g., density and arrangements of myocytes in association with gap-junctional distributions, could constitute important pathologic bases of atrial fibrillation. Integration of these molecular, functional, and morphological features of the myocardium, unveiled by experimental pathological approaches, would pave a new way for understanding pathogenesis of cardiac arrhythmias.

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Section: Arrhthomogenesis Revealed By Functional Imaging Of Non‐electmentioning

confidence: 98%

Section: Roles Of Intracellular Ca 2þ Waves In Triggered Arrhythmiasmentioning

confidence: 99%

Towards an integrated understanding of cardiac arrhythmogenesis − Growing roles of experimental pathology

Tanaka

Matsuyama

Takamatsu

2016

Pathology International

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“…In particular, unknown is whether the [Ca 2+ ] i overload is the only culprit for the contracture. With the advent of live-cell imaging technology, especially in situ real-time confocal microscopy, both the [Ca 2+ ] i dynamics and structure of the individual myocytes can be simultaneously visualized in the working heart [ 14 , 18 , 30 ]. This imaging modality, if applied to the heart under the Ca 2+ -paradox injury, would enable us to address the mechanism(s) underlying development of myocyte contracture.…”

Section: Introductionmentioning

confidence: 99%

How Does the Ca<sup>2+</sup>-paradox Injury Induce Contracture in the Heart?—A Combined Study of the Intracellular Ca<sup>2+</sup> Dynamics and Cell Structures in Perfused Rat Hearts—

Mani

Tanaka

Adachi

et al. 2015

Acta Histochem. Cytochem

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The calcium (Ca2+)-paradox injury of the heart, induced by restoration of extracellular Ca2+ after its short-term depletion, is known to provoke cardiomyocyte contracture. However, undetermined is how the Ca2+-paradox provokes such a distinctive presentation of myocytes in the heart. To address this, we imaged sequential intracellular Ca2+ dynamics and concomitant structures of the subepicardial ventricular myocytes in fluo3-loaded, Langendorff-perfused rat hearts produced by the Ca2+ paradox. Under rapid-scanning confocal microscopy, repletion of Ca2+ following its depletion produced high-frequency Ca2+ waves in individual myocytes with asynchronous localized contractions, resulting in contracture within 10 min. Such alterations of myocytes were attenuated by 5-mM NiCl2, but not by verapamil, SEA0400, or combination of ryanodine and thapsigargin, indicating a contribution of non-specific transmembrane Ca2+ influx in the injury. However, saponin-induced membrane permeabilization of Ca2+ showed no apparent contracture despite the emergence of high-frequency Ca2+ waves, indicating an essential role of myocyte-myocyte and myocyte-extracellular matrix (ECM) mechanical connections in the Ca2+ paradox. In immunohistochemistry Ca2+ depletion produced separation of the intercalated disc that expresses cadherin and dissipation of -dystroglycan located along the sarcolemma. Taken together, along with the trans-sarcolemmal Ca2+ influx, disruption of cell-cell and cell-ECM connections is essential for contracture in the Ca2+-paradox injury.

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“…The entering Ca 2+ triggers release of Ca 2+ from the sarcoplasmic reticulum (SR) through a process known as Ca 2+ ‐induced Ca 2+ release (CICR), which allows a transient increase in the cytosolic [Ca 2+ ] i , that is, a Ca 2+ transient, leading to contraction via Ca 2+ binding to the contractile protein, troponin C. Subsequent membrane repolarization produces decline of [Ca 2+ ] i to the basal (i.e. diastolic) levels by means of re‐uptake of Ca 2+ into the SR by Ca 2+ pump (sarco(endo)plasmic reticulum calcium ATPase (SERCA)) or Ca 2+ extrusion by Ca 2+ pump and Na + /Ca 2+ exchange in the sarcoplasm 27 …”

Section: Arrhythmogenic Disturbance Of Intracellular Calcium Ion Dynamentioning

confidence: 99%

“…The lower image, agonal waves. Reproduced with permission from Takamatsu and Wier (1990) 8 and Tanaka and Takamatsu (2003) 27 . See also Supplementary Movie S1.…”

Section: Arrhythmogenic Disturbance Of Intracellular Calcium Ion Dynamentioning

confidence: 99%

Arrhythmogenic substrates in myocardial infarct

Takamatsu

2008

Pathology International

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Life-threatening ventricular tachyarrhythmias are common clinical complications in ischemic heart diseases, especially infarcted heart. Although electrophysiological mechanisms have been extensively clarified for the genesis of arrhythmias in myocardial infarct, arrhythmogenic substrates in the infarct that eventually lead to electrical derangements are not fully understood. This review focuses on the intracellular calcium ion (Ca2+) dynamics and connexin43 (Cx43) gap junctions that play pivotal roles in excitation/contraction processes and intercellular communication, respectively, in heart muscle cells. Recent development of Ca2+-sensitive fluorescent dyes as well as microscopy imaging techniques has contributed substantially to a more precise understanding of spatiotemporal aspects in the intra- and inter-cellular dynamics of Ca2+ in cardiomyocytes. Ca2+ waves, heterogeneous wave-like elevations of the intracellular Ca2+ concentrations ([Ca2+](i)) that develop under [Ca2+](i)-overloaded conditions of the injured myocardium, play an essential role in arrhythmias, especially in triggered arrhythmias. Alteration of Cx43-mediated electrical coupling, that is, gap junction remodeling that arises at myocyte-myocyte and myocyte-myofibroblast interfaces, would also be an important substrate for arrhythmias, especially re-entrant tachyarrhythmias. Clarification of these substrates would provide not only deeper insights into the upstream events of life-threatening tachyarrhythmias in the infarcted heart but also bases for new therapeutic strategies for cardiovascular diseases.

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Spatiotemporal Visualization of Intracellular Ca2+ in Living Heart Muscle Cells Viewed by Confocal Laser Scanning Microscopy.

Cited by 8 publications

References 70 publications

Towards an integrated understanding of cardiac arrhythmogenesis − Growing roles of experimental pathology

Towards an integrated understanding of cardiac arrhythmogenesis − Growing roles of experimental pathology

How Does the Ca<sup>2+</sup>-paradox Injury Induce Contracture in the Heart?—A Combined Study of the Intracellular Ca<sup>2+</sup> Dynamics and Cell Structures in Perfused Rat Hearts—

Arrhythmogenic substrates in myocardial infarct

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