The network of cardiac KIR2.1: its function, cellular regulation, electrical signaling, diseases and new drug avenues

The functioning of the human heart relies on complex electrical and communication systems that coordinate cardiac contractions and sustain rhythmicity. One of the key players contributing to this intricate system is the K_IR2.1 potassium ion channel, which is encoded by the KCNJ2 gene. K_IR2.1 channels exhibit abundant expression in both ventricular myocytes and Purkinje fibers, exerting an important role in maintaining the balance of intracellular potassium ion levels within the heart. And by stabilizing the resting membrane potential and contributing to action potential repolarization, these channels have an important role in cardiac excitability also. Either gain- or loss-of-function mutations, but also acquired impairments of their function, are implicated in the pathogenesis of diverse types of cardiac arrhythmias. In this review, we aim to elucidate the system functions of K_IR2.1 channels related to cellular electrical signaling, communication, and their contributions to cardiovascular disease. Based on this knowledge, we will discuss existing and new pharmacological avenues to modulate their function.