Biophysical properties of heteromultimeric erg K⁺ channels

Abstract.

The three ether-à-go-go-related gene (erg) K⁺ channel subunits are able to form heteromultimers within their subfamily. The functional importance of this finding is indicated by in situ hybridization experiments showing that the different erg subunits have overlapping expression patterns in several regions of the brain. To investigate the biophysical properties of heteromultimeric erg channels, concatemers of two erg subunits were constructed and expressed heterologously in Chinese hamster ovary (CHO) cells. The resulting currents were measured using the patch-clamp technique. The heteromultimers exhibited an intermediate potential dependence of activation compared with the corresponding wild-type (WT) erg channels. In contrast, the time course of activation was clearly dominated by the faster activating subunit. The kinetics of recovery from inactivation and the deactivation kinetics of all heteromultimers were similar to those of WT erg1 channels, the rat homologue of the human erg1 K⁺ channel (HERG), even if erg1 was not part of the concatemer. Taken together, the biophysical properties of heteromultimeric erg channels result in larger current amplitudes upon both depolarization and repolarization. Thus, through heteromeric assembly erg channels may contribute significantly to different physiological functions such as setting and stabilizing the resting membrane potential and modulation of action potential frequency.