Contractile heterogeneity in ventricular myocardium.

Area of Science:

• Cardiovascular Physiology
• Cellular Biology
• Cardiac Electrophysiology

Background:

• Transmural heterogeneity in ventricular muscle contractility is not well understood.
• Investigating differences in cellular function between endocardial and epicardial myocytes is crucial for understanding overall heart function.

Purpose of the Study:

• To investigate the transmural differences in calcium (Ca2+) transient and sarcomere contraction/relaxation between endocardial and epicardial myocytes.
• To explore the role of CaMKII activity in the frequency-dependent alterations of myocyte contractility.

Main Methods:

• Isolation of endocardial and epicardial myocytes from C57/BL6 mice.
• Simultaneous recording of Ca2+ transient and sarcomere contraction/relaxation at varying stimulation frequencies.
• Western blot analysis to assess CaMKII activity; pharmacological inhibition of CaMKII using KN93.

Main Results:

• Endocardial myocytes exhibit higher baseline diastolic calcium, larger Ca2+ transients, and stronger sarcomere shortening compared to epicardial myocytes.
• Endocardial myocytes show slower Ca2+ transient and sarcomere shortening phases but a more profound frequency-dependent acceleration in relaxation.
• Baseline CaMKII activity is higher in epicardial myocardium, but this heterogeneity reverses with rapid pacing; CaMKII inhibition affects frequency-dependent alterations.

Conclusions:

• Ventricular myocyte contractility is transmurally heterogeneous, with endocardial myocardium being the primary force-generating layer across heart rates.
• Transmural differences in CaMKII activation are critical in mediating the frequency-dependent changes in cardiac contractility.