Dataset Information

Spatiotemporally Non-Uniform Ca2+ Dynamics of Cardiac Purkinje Fibers in Mouse Myocardial Infarct.

ABSTRACT: Surviving Purkinje fibers in myocardial infarct are regarded as an important substrate in arrhythmogenesis. However, poorly understood are functional properties of Purkinje fibers in the infarcted heart. We sought to visualize intracellular Ca2+ ([Ca2+]i) dynamics of Purkinje fiber networks in the mouse myocardial infarct. Using 3- to 4-day-old or 7- to 9-day-old infarcted hearts after the left coronary-artery ligation corresponding, respectively, to acute or healing phase, we conducted rapid fluo4-fluorescence imaging on the endocardial surface of the left ventricular septum by macro-zoom fluorescence microscopy and rapid-scanning confocal microscopy. In contrast with the intact heart, where uniform Ca2+ transients propagated rapidly, the infarcted heart exhibited slow, non-uniform impulse propagations. On confocal microscopy, Purkinje fibers in the peri-infarct zone exhibited non-uniform [Ca2+]i dynamics: beat-to-beat alternans of the Ca2+ transient amplitude in and among the individual fibers, whereas the intact fibers exhibited uniform Ca2+ transients. Such non-uniform [Ca2+]i dynamics were more conspicuous in the acute infarcted hearts than in the healing ones. In accordance with [Ca2+]i dynamics, fixed fluo4-loaded heart preparations exhibited definitive connexin-40 plaques in the peri-infarct Purkinje fibers, whereas the subjacent myocardium presented coagulative necrosis and granulation tissues, respectively. The surviving Purkinje fibers in the peri-infarct zone exhibited non-uniform [Ca2+]i dynamics, which may lead to arrhythmogenesis.

SUBMITTER: Matsuyama TA

PROVIDER: S-EPMC5665107 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Spatiotemporally Non-Uniform Ca2+ Dynamics of Cardiac Purkinje Fibers in Mouse Myocardial Infarct.

Matsuyama Taka-Aki TA Tanaka Hideo H Ishibashi-Ueda Hatsue H Takamatsu Tetsuro T

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20170913 11

Surviving Purkinje fibers in myocardial infarct are regarded as an important substrate in arrhythmogenesis. However, poorly understood are functional properties of Purkinje fibers in the infarcted heart. We sought to visualize intracellular Ca2+ ([Ca2+]i) dynamics of Purkinje fiber networks in the mouse myocardial infarct. Using 3- to 4-day-old or 7- to 9-day-old infarcted hearts after the left coronary-artery ligation corresponding, respectively, to acute or hea ...[more]

PMID: 28903013

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Project description:A crucial issue in understanding cerebellar function is the interaction between simple spike (SS) and complex spike (CS) discharge, the two fundamentally different activity modalities of Purkinje cells. Although several hypotheses have provided insights into the interaction, none fully explains or is completely consistent with the spectrum of experimental observations. Here, we show that during a pseudo-random manual tracking task in the monkey (Macaca mulatta), climbing fiber discharge dynamically controls the information present in the SS firing, triggering robust and rapid changes in the SS encoding of motor signals in 67% of Purkinje cells. The changes in encoding, tightly coupled to CS occurrences, consist of either increases or decreases in the SS sensitivity to kinematics or position errors and are not due to differences in SS firing rates or variability. Nor are the changes in sensitivity due to CS rhythmicity. In addition, the CS-coupled changes in encoding are not evoked by changes in kinematics or position errors. Instead, CS discharge most often leads alterations in behavior. Increases in SS encoding of a kinematic parameter are associated with larger changes in that parameter than are decreases in SS encoding. Increases in SS encoding of position error are followed by and scale with decreases in error. The results suggest a novel function of CSs, in which climbing fiber input dynamically controls the state of Purkinje cell SS encoding in advance of changes in behavior.SIGNIFICANCE STATEMENT Purkinje cells, the sole output of the cerebellar cortex, manifest two fundamentally different activity modalities, complex spike (CS) discharge and simple spike (SS) firing. Elucidating cerebellar function will require an understanding of the interactions, both short- and long-term, between CS and SS firing. This study shows that CSs dynamically control the information encoded in a Purkinje cell's SS activity by rapidly increasing or decreasing the SS sensitivity to kinematics and/or performance errors independent of firing rate. In many cases, the CS-coupled shift in SS encoding leads a change in behavior. These novel findings on the interaction between CS and SS firing provide for a new hypothesis in which climbing fiber input adjusts the encoding of SS information in advance of a change in behavior.

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Dataset Information

Spatiotemporally Non-Uniform Ca2+ Dynamics of Cardiac Purkinje Fibers in Mouse Myocardial Infarct.

Publications

Spatiotemporally Non-Uniform Ca<sup>2+</sup> Dynamics of Cardiac Purkinje Fibers in Mouse Myocardial Infarct.

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