Molecular Determinants of Voltage-Dependent Gating in Kv11.1 Channels

Kv11.1 channels (also known as hERG channels) are voltage-gated K⁺ ion channels that are critical mediators of repolarization in numerous cell types. Their role is best studied in the heart, where they underlie the rapid delayed rectifier current, I_Kr, which supports rhythmic cardiac electrical activity. The importance of this role is highlighted by the association of Kv11.1 channel dysfunction with arrhythmias and sudden death. The critical role of Kv11.1 channels is dependent on their unusual biophysical properties, which produce unique gating behaviors that enable control of membrane repolarization and cellular excitability. In this chapter, we discuss the role of Kv11.1 channels in cellular physiology and how this depends on unique structural features and biophysical function. We then discover what can be learned about Kv11.1 channel gating from studying genetic causes of channel dysfunction. Finally, we consider more recent efforts investigating pharmacological modifiers of Kv11.1 channel gating that may lead to restoration of function and consequently protection against cardiac arrhythmogenicity.