Submitted on February 19, 2006
Accepted on May 8, 2006
Contractile and Ca2+-handling properties of the right ventricular papillary muscle in the late gestation sheep fetus
Timothy N Spencer1, Kimberley J Botting1, Janna L Morrison2, and Giuseppe S. Posterino1*
1 Physiology, Adelaide University, Adelaide, South Australia, Australia; Sansom Institute, University of South Australia, Adelaide, South Australia, Australia
2 Sansom Institute, University of South Australia, Adelaide, South Australia, Australia; Physiology, Adelaide University, Adelaide, South Australia, Australia
* To whom correspondence should be addressed. E-mail: giuseppe.posterino{at}adelaide.edu.au.
The force generating capacity of cardiomyocytes rapidly changes during gestation and early postnatal life coinciding with a transition in cardiomyocyte nucleation in both mice and rats. Changes in nucleation, in turn, appear to coincide with important changes in the excitation-contraction (E-C) coupling architecture. However, it is not clear if similar changes are observed in other mammals where this transition occurs prenatally, such as sheep. Using small (70-300µM diameter) chemically skinned cardiomyocyte bundles from the right ventricular papillary muscle of sheep fetuses at 126-132 and 137-140 days (d) gestational age (GA), we aimed to examine if changes in cardiomyocyte nucleation during late gestation coincided with developmental changes in E-C coupling parameters (e.g. Ca2+-uptake, Ca2+ release and force development). All experiments were conducted at room temperature (23±1°C). We found that the proportion of mononucleate cardiomyocytes decreased significantly with gestational age (126-132d, 45.7±4.7%, n=7; 137-140d, 32.8±1.6%, n=6; p<0.05). When we then examined force development between the two groups, there was no significant difference in either the maximal Ca2+-activated force (6.73±1.54mN/mm2, n=14 vs. 6.55±1.25mN/mm2, n=7, respectively) or the Ca2+-sensitivity of the contractile apparatus (pCa at 50% maximum Ca2+-activated force (EC50): 126-132d, 6.17±0.06, n=14; 137-140d, 6.24±0.08, n=7). However, sarcoplasmic reticulum (SR) Ca2+ uptake rates (but not Ca2+ release) increased with gestational age (P<0.05). These data reveal that during late gestation in sheep when there is a major transition in cardiomyocyte nucleation, SR Ca2+ uptake rates increase which would influence total SR Ca2+ content and force production.
