The GIRK1 Brain Variant GIRK1d and Its Functional Impact on Heteromultimeric GIRK Channels

Abstract

Four isoforms of GIRK channels (GIRK1-4) have been described in humans. In addition, several splice variants of more or less unknown function have been identified from several tissues and species. In our study, we investigated the structure and function of a new variant of GIRK1 that has been isolated from rat brain. Because of wide similarities with a previously described variant, we also named it GIRK1d. This variant lacks a region corresponding to exon 2 of full-length GIRK1, leading to a truncated GIRK1 that lacks the main part of the C-terminus. To study GIRK1d we used the Xenopus laevis expression system, the two-electrode voltage clamp method, and confocal laser scan microscopy. We found that our GIRK1d variant preferentially binds GIRK2 or GIRK4 over GIRK1. Furthermore, it largely reduces conductances mediated by GIRK1/2 or GIRK1/4 hetero-multimeric channels when coexpressed and nearly totally abolishes currents when replacing GIRK1 in hetero-multimeric channels.

Cloning and characterisation of GIRK1 variants resulting from alternative RNA editing of the KCNJ3 gene transcript in a human breast cancer cell line

“…The minimum number of exons in humans is 3 [Schoots et al, 1997]. Molecular cloning of GIRK1 related cRNA's from different species resulted so far in the discovery of five distinct splice variants, not all of them proven to exist in humans [Nelson et al, 1997;Stringer et al, 2001;Zhu et al, 2001;Steinecker et al, 2007]. Eight distinct regions within the humane genome correspond to these sequences ( Fig.…”

GIRK Channel Plasticity and Implications for Drug Addiction

“…The existence of splice variants of the GIRK1 and GIRK2 subunits contributes to the molecular diversity of GIRK channels (Wei et al, 1998;Zhu et al, 2001). Several splice variants of GIRK1 have been described; however, there is limited knowledge about the expression and functional roles of these isoforms (Nelson, Marino, & Allen, 1997;Steinecker, Rosker, & Schreibmayer, 2007;Wagner et al, 2010;Zhu et al, 2001). A number of splice variants of GIRK2 have been identified (Isomoto, Kondo, & Kurachi, 1997;Lesage et al, 1994Lesage et al, , 1995Wei et al, 1998), and three of these isoforms (GIRK2a, GIRK2b, and GIRK2c) are widely expressed in the brain (Isomoto et al, 1997;Wei et al, 1998).…”