The GIRK family of potassium channels mediates important functions in both cardiac and neuronal cells. The channels are composed of subunits that assemble to form a tetratmeric channel; however, how the subunits assemble to form a functional channel is not well known. Studies have shown that subunit interaction promotes proper expression and formation of the channel. Because channels may have variable composition, knowledge of the interaction between subunits may provide additional clues to differential cell function. This proposal is aimed at understanding how subunits interact, and particularly, examining specific regions of the GIRK 1 subunit that affect channel formation and expression. Preliminary data obtained from deletion mutants of GIRK 1 in oocytes suggest that a region of the C-terminus is important for channel function. The applicant will further examine how the wild type subunits interact and how this specific region of the GIRK 1 subunit is involved in the formation of the channel. The last set of experiments will address the role of GIRK 1 in the trafficking of the channel. Knowledge of GIRK channel assembly may provide useful information related to the effects of differential channel expression in specific cell types.
|Sarac, Radmila; Hou, Ping; Hurley, Karen M et al. (2005) Mutation of critical GIRK subunit residues disrupts N- and C-termini association and channel function. J Neurosci 25:1836-46|