Heterogeneous cellular expression of creatine kinase isoenzyme during normal rat heart development

Area of Science:

• Biochemistry
• Developmental Biology
• Cardiovascular Physiology

Background:

• Cardiac creatine kinase (CK) activity undergoes significant changes during heart development.
• The precise mechanisms, particularly the role of CK isoenzyme gene expression, driving these alterations are not fully understood.

Purpose of the Study:

• To investigate how developmental changes in cardiac CK activity relate to alterations in CK isoenzyme gene expression.
• To analyze CK activity and isoenzyme profiles in different cardiac cell types and subcellular fractions during rat heart development.

Main Methods:

• Assessed CK activity and isoenzyme profiles in whole rat heart tissue, isolated muscle and nonmuscle cells, and subcellular fractions (myofibrillar, mitochondrial, cytosolic).
• Utilized electrophoresis for isoenzyme analysis and Arrhenius plots to determine activation energies.
• Compared findings between weanling and adult rat hearts.

Main Results:

• Whole heart CK activity nearly doubled from weanling to adult, primarily due to increased muscle cell activity, while nonmuscle cell activity decreased.
• Myofibrillar and mitochondrial CK activities increased in adult hearts, whereas cytosolic activity remained constant.
• Cardiac muscle cells showed mitochondrial and MM-CK isoforms; nonmuscle cells exhibited mitochondrial, MM, MB, and BB isoforms in weanlings, but lacked BB in adults.
• No changes in CK isoenzyme gene expression were found in cardiac muscle cells; a transition from CK-B to CK-M gene expression occurred in nonmuscle cells.

Conclusions:

• Developmental changes in rat heart CK activity result from the heterogeneous cellular composition and differential subcellular distribution of CK, not altered gene expression in muscle cells.
• The shift in CK isoenzyme gene expression during heart development is confined to nonmuscle cells, transitioning from CK-B to CK-M dominance.