Abstract
The kinetics of contractions and Ca$^2+$ transients are slowed
in myocytes from failing hearts. The mechanisms accounting for these
abnormalities remain unclear. Myocardial infarction (MI) was produced
by ligation of the circumflex artery in rabbits. We used confocal
microscopy to record spatially resolved Ca$^2+$ transients during
field stimulation in left ventricular (LV) myocytes from control
and infarcted hearts (3 weeks). Compared with controls, Ca$^2+$
transients in myocytes adjacent to the infarct had lower peak amplitudes
and prolonged time courses. Control myocytes showed relatively uniform
changes in Ca$^2+$ throughout the cell after electrical stimulation.
In contrast, in MI myocytes Ca$^2+$ increased inhomogeneously
and localized increases in Ca$^2+$ occurred throughout the
rising and falling phases of the Ca$^2+$ transient. Ca$^2+$
content of the sarcoplasmic reticulum did not differ between MI and
control myocytes. Peak L-type Ca$^2+$ current density was reduced
in MI myocytes. The macroscopic gain function was not different in
control and MI myocytes when calculated as the amplitude of the Ca$^2+$
transient/peak I:(Ca). However, when calculated as the peak rate
of rise of the Ca$^2+$ transient/peak I:(Ca), the gain function
was modestly decreased in the MI myocytes. Application of isoproterenol
(100 nmol/L) improved the synchronization of Ca$^2+$ release
in MI myocytes at both 0.5 and 1 Hz. The poorly coordinated production
of Ca$^2+$ sparks in myocytes from infarcted rabbit hearts likely
contributes to the diminished and slowed macroscopic Ca$^2+$
transient. These abnormalities can be largely overcome when phosphorylation
of Ca$^2+$ cycling proteins is enhanced by ss-adrenergic stimulation.
- 11090539
- action
- adrenergic
- animal,
- animals,
- beta-agonists,
- calcium
- calcium,
- channels,
- disease
- dysfunction,
- gov't,
- infarction,
- isoproterenol,
- l-type,
- left,
- male,
- models,
- myocardial
- myocardium,
- non-p.h.s.,
- non-u.s.
- p.h.s.,
- patch-clamp
- potentials,
- processes,
- rabbits,
- research
- reticulum,
- sarcoplasmic
- signaling,
- stochastic
- support,
- techniques,
- u.s.
- ventricular
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