Fhf2 gene deletion causes temperature-sensitive cardiac conduction failure

Area of Science:

• Cardiology
• Molecular Biology
• Physiology

Background:

• Fever is a conserved response to infection, but can impair excitable tissues like the heart.
• Elevated body temperature can lead to cardiac arrhythmias and conduction abnormalities.

Purpose of the Study:

• To investigate the role of fibroblast growth factor homologous factor 2 (FHF2) in temperature-dependent cardiac function.
• To determine the impact of FHF2 deficiency on myocardial excitability and conduction during fever.

Main Methods:

• Utilized genetically modified mice lacking FHF2.
• Measured cardiac rhythm and electrophysiology at baseline and elevated temperatures.
• Performed cardiomyocyte action potential recordings and computational modeling of sodium channel kinetics.

Main Results:

• FHF2-deficient mice exhibited normal cardiac rhythm at baseline but developed conduction failure and ST elevations upon mild temperature increase.
• FHF2-deficient cardiomyocytes were unexcitable at 40°C.
• Absence of FHF2 accelerated sodium channel inactivation, suppressing cardiac sodium currents at higher temperatures.

Conclusions:

• Fibroblast growth factor homologous factor 2 (FHF2) is crucial for maintaining myocardial excitability and conduction during fever.
• FHF2 safeguards the heart against temperature-sensitive conduction failure by regulating sodium channel function.