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Contractile and Ca²⁺-handling properties of the right ventricular papillary muscle in the late-gestation sheep fetus

¹Discipline of Physiology, School of Molecular and Biomedical Science, University of Adelaide, and ²Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia

Submitted 19 February 2006 ; accepted in final form 8 May 2006

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 coupling architecture. However, it is not clear whether similar changes are observed in other mammals in which this transition occurs prenatally, such as sheep. Using small (70–300 µM 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 whether changes in cardiomyocyte nucleation during late gestation coincided with developmental changes in excitation-contraction 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 GA (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 ± 1.54 mN/mm², n = 14 vs. 6.55 ± 1.25 mN/mm², n = 7, respectively) or the Ca²⁺ sensitivity of the contractile apparatus (pCa at 50% maximum Ca²⁺-activated force: 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 GA (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.

cardiomyocytes; excitation-contraction coupling; Ca²⁺ sensitivity