Research Areas

To study the feedback interaction between Ca²⁺ and ionic currents, we further developed the ^selfAP-clamp with Ca²⁺ cycling technique, which preserves Ca²⁺ homeostasis and beat-to-beat contraction under AP-clamp by matching the internal and external physiological solutions. This approach enables studying how Ca²⁺ transient modifies various Ca²⁺-sensitive channels to reshape the action potential and what happens under disease conditions. We discovered that the late Na⁺ current (INaL) recorded under ^selfAP-clamp is significantly larger than previously predicted from V-clamp data; this Na⁺ influx during AP plateau phase can substantially elevate the intracellular [Na⁺] to cause Ca²⁺ overload, which results in spontaneous Ca²⁺ oscillations leading to EADs and DADs. These findings reveal the dual roles of INa in altering APD as an inward current and also altering Na⁺-Ca²⁺ homeostasis as a substantial Na⁺ influx.

Relevant Publications

• Tamas Banyasz, Balazs Horvath, Zhong Jian, Leighton T. Izu, Chen-Izu Y*. Profile of L-type Ca²⁺ current and Na⁺/Ca²⁺ exchange current during a cardiac action potential in ventricular myocytes. Heart Rhythm (2012) 9:134-142. PMID: 21884673 PMC3252888
• Horvath B, Banyasz T, Jian Z, Hegyi B, Kistamas K, Nanasi PP, Izu LT, Chen-Izu Y*. Dynamics of the late Na⁺ current during cardiac action potential and its contribution to afterdepolarizations. J Mol Cell Cardiol. (2013) 64C:59-68. PMID: 24012358 PMC3856763