Contribution of the Kir3.1 subunit to the muscarinic-gated atrial potassium channel IKACh.
The muscarinic-gated atrial potassium (I(KACh)) channel contributes to the heart rate decrease triggered by the parasympathetic nervous system. I(KACh) is a heteromultimeric complex formed by Kir3.1 and Kir3.4 subunits, although Kir3.4 homomultimers have also been proposed to contribute to this conductance. While Kir3.4 homomultimers evince many properties of I(KACh), the contribution of Kir3.1 to I(KACh) is less well understood. Here, we explored the significance of Kir3.1 using knock-out mice. Kir3.1 knock-out mice were viable and appeared normal. The loss of Kir3.1 did not affect the level of atrial Kir3.4 protein but was correlated with a loss of carbachol-induced current in atrial myocytes. Low level channel activity resembling recombinant Kir3.4 homomultimers was observed in 40% of the cell-attached patches from Kir3.1 knock-out myocytes. Channel activity typically ran down quickly, however, and was not recovered in the inside-out configuration despite the addition of GTP and ATP to the bath. Both Kir3.1 knock-out and Kir3.4 knock-out mice exhibited mild resting tachycardias and blunted responses to pharmacological manipulation intended to activate I(KACh). We conclude that Kir3.1 confers properties to I(KACh) that enhance channel activity and that Kir3.4 homomultimers do not contribute significantly to the muscarinic-gated potassium current.
Bettahi
Ilham
I
Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA.
Marker
Cheryl L
CL
Roman
Maria I
MI
Wickman
Kevin
K
D000595:Amino Acid Sequence; D000818:Animals; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D006325:Heart Atria / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic / Q000502:physiology*
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497067:Kcnj3 protein, mouse; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic