Low K+-induced hyperpolarizations trigger transient depolarizations and action potentials in rabbit ventricular...

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Cell Membrane Biology

Background:

• The resting membrane potential (Vrest) of cardiac cells is primarily determined by potassium ion (K+) gradients.
• Understanding how altered extracellular potassium ([K+]o) affects myocyte electrophysiology is crucial for cardiac function.
• Previous studies have explored moderate [K+]o changes, but the impact of extreme reductions requires further investigation.

Purpose of the Study:

• To investigate the electrophysiological effects of large reductions in extracellular potassium ([K+]o) on isolated rabbit ventricular myocytes.
• To elucidate the underlying ionic mechanisms responsible for membrane potential changes under low [K+]o conditions.

Main Methods:

• Whole-cell patch clamp technique applied to isolated rabbit ventricular myocytes.
• Systematic reduction of extracellular potassium ([K+]o) from physiological levels (5.4 mM) to a very low level (0.1 mM).
• Application of voltage clamp pulses and ionic substitutions (La3+, Na+, Cl-) to probe current mechanisms.

Main Results:

• Decreasing [K+]o to 0.1 mM caused significant hyperpolarization of Vrest (from -75.6 to -140.3 mV).
• Low [K+]o induced irregular transient depolarizations and elicited action potentials in over 50% of trials.
• Lanthanum (La3+) partially reversed these effects, suggesting involvement of potassium currents and potentially calcium or other cation influx.

Conclusions:

• Large reductions in [K+]o profoundly alter cardiac myocyte membrane potential and excitability.
• The observed effects are attributed to a decrease in the inward rectifier potassium current (IK1) and the emergence of inward currents, possibly due to electroporation.
• These findings provide insights into arrhythmogenesis under conditions of severe hypokalemia.