Abstract
Two genetic experimental approaches, de novo expression of parvalbumin
(Parv) and overexpression of sarco(endo)plasmic reticulum Ca$^2+$-ATPase
(SERCA2a), have been shown to increase relaxation rates in myocardial
tissue. However, the relative effect of Parv and SERCA2a on systolic
function and on beta-adrenergic responsiveness at varied pacing rates
is unknown. We used gene transfer in isolated rat adult cardiac myocytes
to gain a fuller understanding of Parv/SERCA2a function. As demonstrated
previously, when Parv is expressed in elevated concentration (>0.1
mM), the transduced myocytes showed a reduction in sarcomere-shortening
amplitude: 129 +/- 17, 81 +/- 8, and 149 +/- 14 nm for control, Parv,
and SERCA2a, respectively. At physiological temperature, shortening
amplitude responses of Parv and SERCA2a myocytes to the beta-adrenergic
agonist isoproterenol (Iso) were not statistically different from
that of control myocytes. However, in SERCA2a myocytes, in which
baseline was slightly elevated and the Iso-stimulated value was slightly
lower, the increase in shortening was slightly less than in Parv
or control myocytes: 108 +/- 14, 169 +/- 39, and 34 +/- 12\% for
control, Parv, and SERCA2a, respectively. In another test set, Parv
myocytes had the strongest early postrest potentiation among all
groups studied (rest time = 2-10 s), and SERCA2a myocytes were the
least sensitive to variations in stimulation rhythm. To replicate
the deficient Ca$^2+$ removal observed in heart failure, we used
150 nM thapsigargin. Under these conditions, control myocytes exhibited
slowed relaxation, whereas Parv myocytes retained their rapid kinetics,
showing that Parv is still able to control relaxation, even when
SERCA2a function is impaired.
- 15331372
- adrene,
- animals,
- atpase,
- beta-agonists,
- calcium,
- cardiac,
- cells,
- contraction,
- cultured,
- diastole,
- expression,
- female,
- gene
- isoproterenol,
- myocardial
- myocytes,
- parvalbumins,
- rats,
- rgic
- sprague-dawley,
- techniques,
- transfer
- {c}a$^{2+}$-transporting
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