HERG - Biological Function

Biological Function

hERG forms the major portion of one of the ion channel proteins (the 'rapid' delayed rectifier current (I_Kr)) that conducts potassium (K+) ions out of the muscle cells of the heart (cardiac myocytes), and this current is critical in correctly timing the return to the resting state (repolarization) of the cell membrane during the cardiac action potential. Sometimes, when referring to the pharmacological effects of drugs, the terms "hERG channels" and I_Kr are used interchangeably, but, in the technical sense, "hERG channels" can be made only by scientists in the laboratory; in formal terms, the naturally-occurring channels in the body that include hERG are referred to by the name of the electrical current that has been measured in that cell type, so, for example, in the heart, the correct name is I_Kr. This difference in nomenclature becomes clearer in the controversy as to whether the channels conducting I_Kr include other subunits (e.g., beta subunits) or whether the channels include a mixture of different types (isoforms) of hERG, but, when the originally-discovered form of hERG is experimentally transferred into cells that previously lacked hERG (i.e., heterologous expression), a potassium ion channel is formed, and this channel has many signature features of the cardiac 'rapid' delayed rectifier current (I_Kr), including I_Kr's inward rectification that results in the channel producing a 'paradoxical resurgent current' in response to repolarization of the membrane.