Cardiomyocyte ionic currents in intact young and aged murine Pgc-1β^-/- atrial preparations

Area of Science:

• Cardiovascular Physiology
• Cardiac Electrophysiology
• Mitochondrial Biology

Background:

• Energetically deficient Pgc-1β knockout mouse hearts exhibit age-dependent atrial arrhythmias.
• These arrhythmias are linked to slowed action potential (AP) conduction and reduced AP upstroke rates.

Purpose of the Study:

• To investigate the role of sodium (Na+) current alterations in the electrophysiological phenotypes of Pgc-1β knockout mouse hearts.
• To determine if altered Na+ or potassium (K+) currents underlie slowed conduction and arrhythmogenicity.

Main Methods:

• Loose patch-clamp recordings were performed on atrial cardiomyocytes from young and aged wild-type (WT) and Pgc-1β knockout mice.
• In vivo conditions were preserved to accurately assess voltage-dependent Na+ and K+ currents.

Main Results:

• Peak Na+ current was significantly reduced in Pgc-1β knockout hearts, independent of age.
• No significant differences in Na+ current activation/inactivation kinetics or K+ current properties were observed between genotypes or ages.
• These findings implicate reduced Na+ current as the primary electrophysiological alteration.

Conclusions:

• Reduced Na+ current, not K+ current, is a key mechanism causing slowed atrial conduction in Pgc-1β knockout hearts.
• This mechanism contributes to the observed age-dependent atrial arrhythmogenicity, relevant to clinical conditions.