Cellular and subcellular alternans in the canine left ventricle

Area of Science:

• Cardiology
• Cell Physiology
• Biophysics

Background:

• Action potential duration (APD) alternans in the canine left ventricle (LV) is known to initiate in endocardial (END) and midmyocardial (MID) regions.
• Epicardial (EPI) regions are less susceptible to APD alternans compared to ENDO and MID regions.

Purpose of the Study:

• To investigate regional disparities in the rate-dependent characteristics of Ca(2+) transients.
• To evaluate the role of the sarcoplasmic reticulum (SR) in the development of Ca(2+) transient alternans.

Main Methods:

• Studies utilized isolated canine LV myocytes (ENDO, MID, EPI) and LV wedge preparations.
• Ca(2+) transients were measured using confocal microscopy under field stimulation or voltage clamp.
• Experiments involved varying basic cycle lengths (BCL) to induce alternans.

Main Results:

• Ca(2+) transient alternans predominantly appeared in ENDO and MID regions at slower pacing rates compared to EPI.
• EPI cells exhibited Ca(2+) transient alternans at shorter BCLs than MID and ENDO cells.
• Subcellular alternans of Ca(2+) transient amplitude also occurred earlier in EPI cells with increased pacing.

Conclusions:

• Distinct regional differences exist in canine LV vulnerability to rate-dependent Ca(2+) alternans, linked to SR function and Ca(2+) cycling.
• Development of subcellular Ca(2+) alternans indicates intracellular heterogeneities in Ca(2+) cycling.
• Neonatal myocytes' inability to develop Ca(2+) alternans supports the critical role of SR Ca(2+) cycling in these phenomena.