Developmental Changes in the Regulation of Contractions in Human Fetal Cardiac Myocytes. † 100

We studied developmental changes in the mechanisms regulating contractions in 1^st and 2^nd trimester human fetal hearts. We hypothesize sarcolemmal Ca²⁺ influx is the dominant mechanism for contractions early in human cardiac development, while Ca²⁺ release from the sarcoplasmic reticulum develops later in the fetal period. To test our hypothesis, we measured field-stimulated contractions in cultured 1^st trimester and freshly isolated 2^nd trimester cardiac myocytes, and obtained electron micrographs of fetal hearts from the same age groups, obtained under approved institutional guidelines. While contractions after 10μM ryanodine were unchanged in myocyte clusters from 1^st trimester hearts, they were depressed in ventricular myocytes from 2^nd trimester hearts. Contractions in myocytes from both age groups were eliminated after 20μM nifedipine. Electron micrographs from 1^st trimester hearts demonstrated 1 or rarely 2 rows of myofibrils in the subsarcolemmal regions of ventricular myocytes, and indistinct A and I bands. T-tubules and sarcoplasmic reticulum were not seen. Myofibrillar organization and density increased during the 2^nd trimester, and structures consistent with caveolae and rudimentary longitudinal and corbular sarcoplasmic reticulum were identified. Thus, Ca²⁺ influx through the Ca²⁺ channels is important for contractions in 1^st and 2^nd trimester human fetal hearts. The sarcoplasmic reticulum contributes to contractions in the 2^nd trimester.