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Impaired cell shortening and relengthening with increased pacing frequency are intrinsic to the senescent mouse cardiomyocyte.

Abstract：

:Increased heart rate enhances cardiac contractility and accelerates relaxation. Both the force- and relaxation-frequency relationships are critical to myocardial function, especially during stress, and have been shown to be impaired in senescent myocardium. While senescent myocardium is characterized by decreased sarcoplasmic reticulum calcium ATPase activity, it is unclear if altered calcium regulation is directly responsible for the attenuated contractility and relaxation observed with increasing pacing frequency in aged myocardium. We examined this issue using freshly dissociated left ventricular myocytes, isolated from young adult and senescent mouse hearts. Myocytes were paced from 2 to 9 Hz at 37 degrees C, and cell shortening and [Ca(2+)](i)were simultaneously measured using video edge-detection and fura-2 fluorescence, respectively. In adult myocytes, increasing the pacing rate resulted in a progressive increase in percent cell shortening (CS) (P<0.01). This positive CS-frequency relationship was paralleled by an increase in [Ca(2+)](i)transient amplitude (P<0.05). In contrast, the CS-frequency relationship was blunted in senescent myocytes with no increase in percent CS or [Ca(2+)](i)transient amplitude with increasing pacing rate. With increased pacing, the decreases in time constants (tau) of cell relengthening and Ca(2+)transient decay were much steeper in adult compared to senescent myocytes (P<0.05). This study demonstrates that adult mouse myocytes exhibit augmented intracellular Ca(2+)transient amplitude and enhanced intracellular Ca(2+)removal with increasing pacing frequency, resulting in increased cell shortening and enhanced relengthening with frequency. In contrast, senescent mouse myocytes exhibit impaired calcium handling with increasing pacing frequency, which correlated with impairment of both cell shortening and relengthening.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Lim CC,Apstein CS,Colucci WS,Liao R

doi

10.1006/jmcc.2000.1239

keywords:

subject

Has Abstract

pub_date

2000-11-01 00:00:00

pages

2075-82

issue

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(00)91239-2

journal_volume

pub_type

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Impaired cell shortening and relengthening with increased pacing frequency are intrinsic to the senescent mouse cardiomyocyte.