Na+ channel modulation and force-frequency relationship in human myocardium

Area of Science:

• Cardiology
• Physiology
• Molecular Biology

Background:

• Force of contraction (FOC) enhancement with increased stimulation frequency is a key positive inotropic mechanism in human myocardium.
• Understanding the role of sodium (Na+) influx in this frequency-force relationship (FFR) is critical for cardiac health.

Purpose of the Study:

• To investigate how alterations in Na+ influx influence FFR in human myocardium.
• To determine the effects of increased and decreased Na+ influx on force potentiation and diastolic tension.

Main Methods:

• Isometric FOC of human right auricular trabeculae (n=12) was measured at varying stimulation rates (0.5-3 Hz).
• Experiments were conducted under control conditions, after increasing Na+ influx with (+/-)BDF 9148 (BDF), and after decreasing Na+ influx with lidocaine (LIDO).
• Rate-dependent changes in diastolic tension (DT) were also recorded.

Main Results:

• Increased Na+ influx (BDF) decreased the optimal stimulation frequency (SFmax) and maximal force potentiation (PIEmax).
• Decreased Na+ influx (LIDO) increased SFmax and PIEmax compared to control.
• Enhanced Na+ influx (BDF) led to increased diastolic tension at higher rates, unlike control or LIDO conditions.

Conclusions:

• Na+ influx, alongside Ca2+ handling, significantly influences frequency-induced force potentiation in human myocardium.
• Altered Na+ influx can impact myocardial contractility, potentially contributing to negative FFR observed in diseased hearts.
• Na+ homeostasis plays a vital role in regulating cardiac contractility in response to stimulation frequency.