I(NaCa) contributes to electrical heterogeneity within the canine ventricle

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Cellular Biology

Background:

• The sodium-calcium exchanger (NCX) plays a critical role in regulating intracellular calcium concentrations.
• Transmural differences in myocyte properties contribute to cardiac electrical heterogeneity.
• Understanding I(NaCa) is crucial for comprehending normal and pathological cardiac function.

Purpose of the Study:

• To investigate the amplitude of sodium-calcium exchange current (I(NaCa)) across different layers of the canine ventricular wall.
• To determine if transmural variations in I(NaCa) contribute to electrical heterogeneity in the heart.

Main Methods:

• Whole-cell voltage-clamp techniques were employed to record currents in isolated canine ventricular myocytes (epicardial, midmyocardial, endocardial) at 37°C.
• Potassium, calcium-activated chloride, and sodium-pump currents were excluded.
• I(NaCa) was activated by either calcium release from the sarcoplasmic reticulum or rapid removal of external sodium.

Main Results:

• I(NaCa) amplitude was significantly larger in midmyocardial myocytes compared to endocardial myocytes, irrespective of the activation method.
• When activated by the calcium transient, I(NaCa) values at -80 mV were -0.316 ± 0.013, -0.293 ± 0.016, and -0.210 ± 0.007 pC/pF for midmyocardial, epicardial, and endocardial myocytes, respectively.
• When triggered by sodium removal, peak I(NaCa) was 0.74 ± 0.04, 0.57 ± 0.04, and 0.50 ± 0.03 pA/pF in midmyocardial, epicardial, and endocardial myocytes, respectively.
• Epicardial I(NaCa) was smaller than midmyocardial I(NaCa) upon sodium removal, but comparable when activated by the calcium transient, suggesting transmural differences in excitation-contraction coupling.

Conclusions:

• Significant transmural gradients in I(NaCa) exist in canine ventricular myocytes.
• These I(NaCa) differences contribute to electrical heterogeneity under normal and pathological conditions.
• A pronounced midmyocardial I(NaCa) may influence action potential duration and predispose to triggered activity under calcium-overload states.