Regular Article
Heterologous Multimeric Assembly Is Essential for K+ Channel Activity of Neuronal and Cardiac G-Protein-Activated Inward Rectifiers

https://doi.org/10.1006/bbrc.1995.2019Get rights and content

Abstract

The family of G-protein-activated inward-rectifiers K+ channels presently comprise at least 3 cloned members called GIRK1, GIRK2 and GIRK3. A close structural parent of GIRK channels has recently been described as being an ATP-sensitive K+ channel. This paper shows that Xenopus expression of this new channel that we call GIRK4 does not produce an ATP-inhibitable activity with a pharmacological activation by pinacidil as previously described but instead a G-protein activated inward-rectifier. While oocyte expression of single subunits is infrequent and relatively modest in intensity, expression of GIRK1,2, GIRK1,4 and GIRK2,4 mixtures leads to routine and robust expression of K+ channels indicating that heterologous subunit assembly is necessary for activity. Activity of GIRK1,2 GIRK1,4 and GIRK2,4 channels required the presence of ATP acting as an activator at the cytoplasmic face and is further activated by the βγ subunits.

References (0)

Cited by (133)

  • Structural Insights into GIRK Channel Function

    2015, International Review of Neurobiology
    Citation Excerpt :

    Using heterologous expression systems and biochemical measurements, the IKACh channel was determined to be a heterotetramer composed of GIRK1 and GIRK4 subunits (Krapivinsky, Gordon, et al., 1995), while brain GIRK channels were heterotetramers of GIRK1 and GIRK2, GIRK1 and GIRK3, or GIRK2 and GIRK3 (Jelacic, Kennedy, Wickman, & Clapham, 2000; Jelacic, Sims, & Clapham, 1999; Krapivinsky, Gordon, et al., 1995). Only GIRK2 and GIRK4 subunits also form functional homotetramers in the brain and heart, respectively (Duprat et al., 1995; Jelacic et al., 2000; Karschin, Dissmann, Stuhmer, & Karschin, 1996; Kobayashi et al., 1995; Kofuji et al., 1995; Lesage et al., 1994; Liao, Jan, & Jan, 1996). For GIRK2, there are four splice variants, termed GIRK2a–d (Inanobe et al., 1999; Isomoto et al., 1996; Lesage et al., 1994, 1995; Wei et al., 1998; Wickman, Pu, & Clapham, 2002), of which GIRK2a–c are expressed in the brain and GIRK2d in the testes.

  • New pharmacological approaches to atrial fibrillation

    2012, Drug Discovery Today
    Citation Excerpt :

    The acetylcholine-activated inward rectifier potassium current (IKACh) is found predominantly in the supraventricular regions and conduction (Purkinje) system of the heart. Conducting IKACh is a heterotetrameric channel composed of Kir3.1/3.4 subunits [17,18]. Activation of this current shortens the atrial APD and AERP and reduces the rate of diastolic depolarisation in nodal tissues (negatively chronotropic and dromotropic).

  • Kir3.1 inwardly rectifying potassium channel

    2007, xPharm: The Comprehensive Pharmacology Reference
  • G-protein-gated inwardly rectifying potassium channels regulate ADP-induced cPLA<inf>2</inf> activity in platelets through Src family kinases

    2006, Blood
    Citation Excerpt :

    Mammalian cells express 4 different GIRK subunits, GIRK1-4. Functional GIRK channels exist as homo- or heterotetrameric channels, composed of 4 similar or dissimilar subunits,26-29 for example, GIRK1/4 and GIRK4/4 are present in the heart, whereas GIRK2/3 and GIRK1/2 complexes are prevalent in the brain. GIRK2, -3, and -4 can form functional homomultimers, while GIRK1 requires the coassociation with GIRK2, -3, or -4 to achieve membrane surface expression and for the formation of functional channels.

View all citing articles on Scopus
View full text