ERG proteins and functional cardiac I-Kr channels in rat, mouse, and humanheart

The voltage-gated K+ channel (Kv) pore forming a subunit, ERG1 (KCNH2), has been identified as the locus of mutations in one type of inherited long QT syndrome, LQT2. Heterologous expression of ERG1 reveals rapidly activating and inactivating K+ currents, characterized by marked inward rectification at potentials positive to 0 mV, which are similar to the rapid component o f cardiac delayed rectification I-Kr. There are, however, marked difference s in the properties of expressed ERG1 and endogenous cardiac I-Kr, suggesti ng that functional I-Kr channels reflect the coassembly of full-length ERG1 with splice variants and/or accessory subunits. Consistent with these hypo theses, N- and C-terminal variants of ERG1 have been identified, and it has been demonstrated that heterologously expressed ERG1 and minK (or MiRP1) c oimmunoprecipitate. Recent biochemical studies, however, suggest that only full-length ERG1 is expressed in adult mouse, rat, or human heart. Clearly, further studies, focused on identifying the subunits that coassemble with ERG1 in vivo, as well as on post-translational processing of the full-lengt h ERG1 protein will be necessary to define the molecular composition of fun ctional cardiac I-Kr channels. (Trends Cardiovasc Med 2001; 11:286-294). (C ) 2001, Elsevier Science Inc.