Krapivinsky, G., Gordon, E. A., Wickman, K., Velimirovic, B., Krapivinsky, L. & Clapham, D. E. The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K+-channel proteins. Nature 374, 135-141
Heart rate is slowed in part by acetylcholine-dependent activation of a cardiac potassium (K+) channel, IKACh. Activated muscarinic receptors stimulate IKACh via the G-protein beta gamma-subunits. It has been assumed that the inwardly rectifying K(+)-channel gene, GIRK1, alone encodes IKACh. It is now shown that IKACh is a heteromultimer of two distinct inwardly rectifying K(+)-channel subunits, GIRK1 and a newly cloned member of the family, CIR.
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"On the other hand, it has been previously shown that expression of either Kir3.1 or Kir3.4 homomers fails to display similar channel activity as the heteromeric complex. Specifically, homomeric expression of Kir3.1 in several mammalian cell lines does not yield detectable currents (e.g.,   ). Furthermore, homomeric expression of Kir3.4 gives several-fold smaller currents than the Kir3.1/Kir3.4 "
"Atrial-specific currents I Kur and I K,ACh are functional in hESC-atrial CMs The potassium ion channels K v 1.5 and the K ir 3.1/3.4 are more abundant in human atrial than in ventricular CMs (Wang et al, 1993; Krapivinsky et al, 1995) and are responsible for functional differences between the two chambers. K v 1.5, encoded by the gene KCNA5, conducts the ultrarapid delayed rectifier K + current, I Kur, which is a major repolarizing current in the human atrium. "
"that early interactions with signaling partners such as Gβγ play in channel maturation remain unclear. When expressed alone, recombinant Kir3.1, which contains only one potential site for Nlinked glycosylation, migrates as a doublet with a molecular mass of 54 and 56 kDa, with the upper band being the core-glycosylated, immature form of the protein (Krapivinsky et al., 1995a; Kennedy et al., 1999). Upon treatment with either endoglycosidase H, an enzyme that selectively removes N-linked glycosyl moieties from proteins that have not been processed in the Golgi, or endoglycosidase F, an enzyme that non-selectively removes all N-linked sugar residues, the 56 kDa band is virtually abolished, confirming its residence in the ER (Kennedy et al., 1999). "
[Show abstract][Hide abstract] ABSTRACT: The role of Gβγ subunits in Kir3 channel gating is well characterized. Here, we have studied the role of Gβγ dimers during their initial contact with Kir3 channels, prior to their insertion into the plasma membrane. We show that distinct Gβγ subunits play an important role in orchestrating and fine-tuning parts of the Kir3 channel life cycle. Gβ1γ2, apart from its role in channel opening that it shares with other Gβγ subunit combinations, may play a unique role in protecting maturing channels from degradation as they transit to the cell surface. Taken together, our data suggest that Gβ1γ2 prolongs the lifetime of the Kir3.1/Kir3.2 heterotetramer, although further studies would be required to shed more light on these early Gβγ effects on Kir3 maturation and trafficking.