. 2019 Mar 14;3(1):010901. doi: 10.1063/1.5070106

TABLE II.

Key measurements of maturity. Properties and references are outlined in Table I.

Contractile force and kinetics

Mature cardiomyocytes produce higher forces and have faster upstroke and decay rates. Changes in sarcomere proteins and their organization, calcium handling, t-tubule organization, ion channel expression, and ECM binding all influence contractile force and kinetics.

Response to adrenergic stimulation

In mature cardiomyocytes, there is a chronotropic, lusitropic, and inotropic response to adrenergic stimulation. Changes in sarcomere proteins and their organization, calcium handling, t-tubule organization, and ion channel expression all influence this response.

Increased force-frequency relationship

Mature cardiomyocytes increase force as their rate increases (positive staircase). This is heavily influenced by the proteins involved in calcium handling and cellular compartment organization.

Conduction velocity

Electrical conduction velocity is faster in mature cardiomyocytes. This is regulated by cardiomyocyte coupling via cell-cell connections and gap junctions and by ion channel expression and regulation. Additionally, resting membrane potential of the cardiomyocytes influences this property.

Transcriptome

The adult cardiomyocyte transcriptome is distinct from an immature cardiomyocyte. There are extensive changes in expression of sarcomeric protein isoforms, metabolic genes, and cell cycle genes during this process.⁶⁵ The transcriptome can be potentially used as an unbiased holistic measure of maturity^40,66 but should be used in combination with functional assays.

Metabolism

During maturation, there is a switch from glycolysis to fatty acid metabolism. This facilitates a high metabolic capacity and increased mitochondrial biogenesis.