Patch-Clamp Recordings of Action Potentials From Human Atrial Myocytes: Optimization Through Dynamic Clamp

Area of Science:

• Cardiovascular Physiology
• Electrophysiology

Background:

• Atrial fibrillation (AF) is a common arrhythmia, necessitating new treatments.
• Accurate action potential (AP) measurements in human atrial myocytes are crucial for developing novel AF therapies.
• Isolated human atrial myocytes often exhibit depolarized resting membrane potentials (RMP), hindering reliable AP recordings.

Purpose of the Study:

• To evaluate the efficacy of dynamic clamp using synthetic inward rectifier K+ current (I_K1) to stabilize RMP in isolated human atrial myocytes.
• To determine the optimal I_K1 rectification for improving AP recordings and facilitating drug screening.

Main Methods:

• Human atrial myocytes were isolated from patients undergoing cardiac surgery.
• Perforated patch-clamp technique was used to record APs with dynamic clamp-mediated I_K1 injection.
• Synthetic I_K1 with strong or moderate rectification, or constant current, was injected to establish a stable RMP.
• The effects of various ion channel blockers on AP characteristics were assessed.

Main Results:

• Dynamic clamp successfully stabilized RMP in depolarized myocytes, enabling AP elicitation.
• AP duration varied significantly based on the current injection method; moderate I_K1 rectification yielded APD closest to native non-depolarized cells.
• Injected I_K1 maintained the functional integrity of major ionic currents, as evidenced by drug sensitivity.

Conclusions:

• Dynamic clamp with synthetic I_K1, particularly with moderate rectification, significantly improves AP recordings in human atrial myocytes.
• This technique provides a reliable platform for assessing the efficacy of novel antiarrhythmic compounds.
• Dynamic clamp is a valuable tool for advancing research in cardiac electrophysiology and drug discovery.