Rat and mouse cardiomyocytes show subtle differences in creatine kinase expression and compartmentalization

Area of Science:

• Cardiology
• Cellular Metabolism
• Biochemistry

Background:

• Creatine kinase (CK) and adenylate kinase (AK) are key energy transfer systems in cardiomyocytes.
• Previous studies on permeabilized cardiomyocytes yielded ambiguous results regarding ADP channeling from AK and mitochondrial CK to stimulate respiration.

Purpose of the Study:

• To directly compare the CK and AK systems in rat and mouse hearts.
• To investigate ADP channeling efficiency and its impact on mitochondrial respiration in different species.

Main Methods:

• Assessed CK and AK activities and CK isoform distribution in heart homogenates.
• Measured mitochondrial respiration (VO2_CK, VO2_AK) in permeabilized cardiomyocytes.
• Evaluated ADP channeling by inhibiting respiration with PEP and PK.

Main Results:

• Rat hearts exhibited lower aerobic capacity and higher VO2_CK/VO2_max compared to mouse hearts.
• Despite a higher fraction of mitochondrial CK in rats, less ADP was channeled from CK to mitochondria, suggesting species-specific intracellular compartmentalization.
• Adenylate kinase (AK) did not channel ADP to mitochondria in either species, and AK- and CK-activities in homogenates were significantly higher than estimated ADP-phosphorylation rates in permeabilized cells.

Conclusions:

• Significant differences in intracellular compartmentalization of energy transfer systems exist between rat and mouse cardiomyocytes.
• Energetic compartmentalization plays a critical role in cardiac metabolic regulation and signaling, impacting cellular energy dynamics.