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Synergistic activation of G protein-gated inwardly rectifying potassium channels by the betagamma subunits of G proteins and Na(+) and Mg(2+) ions.

Petit-Jacques J, Sui JL, Logothetis DE - J. Gen. Physiol. (1999)

Bottom Line: Native and recombinant G protein-gated inwardly rectifying potassium (GIRK) channels are directly activated by the betagamma subunits of GTP-binding (G) proteins.The presence of phosphatidylinositol-bis-phosphate (PIP(2)) is required for G protein activation.At high levels of PIP(2), synergistic interactions among Na(+), Mg(2+), and G(betagamma) subunits resulted in severalfold stimulated levels of channel activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Mount Sinai School of Medicine of the New York University, New York, New York 10029, USA.

ABSTRACT
Native and recombinant G protein-gated inwardly rectifying potassium (GIRK) channels are directly activated by the betagamma subunits of GTP-binding (G) proteins. The presence of phosphatidylinositol-bis-phosphate (PIP(2)) is required for G protein activation. Formation (via hydrolysis of ATP) of endogenous PIP(2) or application of exogenous PIP(2) increases the mean open time of GIRK channels and sensitizes them to gating by internal Na(+) ions. In the present study, we show that the activity of ATP- or PIP(2)-modified channels could also be stimulated by intracellular Mg(2+) ions. In addition, Mg(2+) ions reduced the single-channel conductance of GIRK channels, independently of their gating ability. Both Na(+) and Mg(2+) ions exert their gating effects independently of each other or of the activation by the G(betagamma) subunits. At high levels of PIP(2), synergistic interactions among Na(+), Mg(2+), and G(betagamma) subunits resulted in severalfold stimulated levels of channel activity. Changes in ionic concentrations and/or G protein subunits in the local environment of these K(+) channels could provide a rapid amplification mechanism for generation of graded activity, thereby adjusting the level of excitability of the cells.

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Related in: MedlinePlus

A model depicting gating of GIRK channels by the combination of PIP2 with gating molecules Gβγ and/or Na+ and Mg2+ ions. (Co) Channel closed state, in the absence of PIP2 in the plasma membrane and gating molecules. (C1) Channel closed state, in the presence of PIP2 in the membrane GIRK channels experience weak interactions that in the absence of gating molecules are not of sufficient strength to gate the channel. (C2) Channel closed state, gating molecules can interact with the channel at distinct sites but in the absence of PIP2 they fail to gate the channel. (O) Channel open state, gating molecules in the presence of membrane PIP2 can activate the channel and show synergism.
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Figure 8: A model depicting gating of GIRK channels by the combination of PIP2 with gating molecules Gβγ and/or Na+ and Mg2+ ions. (Co) Channel closed state, in the absence of PIP2 in the plasma membrane and gating molecules. (C1) Channel closed state, in the presence of PIP2 in the membrane GIRK channels experience weak interactions that in the absence of gating molecules are not of sufficient strength to gate the channel. (C2) Channel closed state, gating molecules can interact with the channel at distinct sites but in the absence of PIP2 they fail to gate the channel. (O) Channel open state, gating molecules in the presence of membrane PIP2 can activate the channel and show synergism.

Mentions: Channel binding sites for PIP2, Gβγ, and Na2+ ions have been identified (Huang et al. 1995; Huang et al. 1997; Kunkel and Peralta 1995; He et al. 1999). We postulate that additional distinct sites exist to completely account for the effects of gating molecules on channel activity. Fig. 8 shows the closed channel state C0 in the absence of PIP2. GIRK channels interact weakly with PIP2, and as a result PIP2 does not directly activate these channels (closed state C1). In the absence of PIP2, gating molecules such as Gβγ, Na+, or Mg2+ are unable to activate the channel (closed state C2). However, in the presence of PIP2, any of the gating molecules can cause channel activation.


Synergistic activation of G protein-gated inwardly rectifying potassium channels by the betagamma subunits of G proteins and Na(+) and Mg(2+) ions.

Petit-Jacques J, Sui JL, Logothetis DE - J. Gen. Physiol. (1999)

A model depicting gating of GIRK channels by the combination of PIP2 with gating molecules Gβγ and/or Na+ and Mg2+ ions. (Co) Channel closed state, in the absence of PIP2 in the plasma membrane and gating molecules. (C1) Channel closed state, in the presence of PIP2 in the membrane GIRK channels experience weak interactions that in the absence of gating molecules are not of sufficient strength to gate the channel. (C2) Channel closed state, gating molecules can interact with the channel at distinct sites but in the absence of PIP2 they fail to gate the channel. (O) Channel open state, gating molecules in the presence of membrane PIP2 can activate the channel and show synergism.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2230539&req=5

Figure 8: A model depicting gating of GIRK channels by the combination of PIP2 with gating molecules Gβγ and/or Na+ and Mg2+ ions. (Co) Channel closed state, in the absence of PIP2 in the plasma membrane and gating molecules. (C1) Channel closed state, in the presence of PIP2 in the membrane GIRK channels experience weak interactions that in the absence of gating molecules are not of sufficient strength to gate the channel. (C2) Channel closed state, gating molecules can interact with the channel at distinct sites but in the absence of PIP2 they fail to gate the channel. (O) Channel open state, gating molecules in the presence of membrane PIP2 can activate the channel and show synergism.
Mentions: Channel binding sites for PIP2, Gβγ, and Na2+ ions have been identified (Huang et al. 1995; Huang et al. 1997; Kunkel and Peralta 1995; He et al. 1999). We postulate that additional distinct sites exist to completely account for the effects of gating molecules on channel activity. Fig. 8 shows the closed channel state C0 in the absence of PIP2. GIRK channels interact weakly with PIP2, and as a result PIP2 does not directly activate these channels (closed state C1). In the absence of PIP2, gating molecules such as Gβγ, Na+, or Mg2+ are unable to activate the channel (closed state C2). However, in the presence of PIP2, any of the gating molecules can cause channel activation.

Bottom Line: Native and recombinant G protein-gated inwardly rectifying potassium (GIRK) channels are directly activated by the betagamma subunits of GTP-binding (G) proteins.The presence of phosphatidylinositol-bis-phosphate (PIP(2)) is required for G protein activation.At high levels of PIP(2), synergistic interactions among Na(+), Mg(2+), and G(betagamma) subunits resulted in severalfold stimulated levels of channel activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Mount Sinai School of Medicine of the New York University, New York, New York 10029, USA.

ABSTRACT
Native and recombinant G protein-gated inwardly rectifying potassium (GIRK) channels are directly activated by the betagamma subunits of GTP-binding (G) proteins. The presence of phosphatidylinositol-bis-phosphate (PIP(2)) is required for G protein activation. Formation (via hydrolysis of ATP) of endogenous PIP(2) or application of exogenous PIP(2) increases the mean open time of GIRK channels and sensitizes them to gating by internal Na(+) ions. In the present study, we show that the activity of ATP- or PIP(2)-modified channels could also be stimulated by intracellular Mg(2+) ions. In addition, Mg(2+) ions reduced the single-channel conductance of GIRK channels, independently of their gating ability. Both Na(+) and Mg(2+) ions exert their gating effects independently of each other or of the activation by the G(betagamma) subunits. At high levels of PIP(2), synergistic interactions among Na(+), Mg(2+), and G(betagamma) subunits resulted in severalfold stimulated levels of channel activity. Changes in ionic concentrations and/or G protein subunits in the local environment of these K(+) channels could provide a rapid amplification mechanism for generation of graded activity, thereby adjusting the level of excitability of the cells.

Show MeSH
Related in: MedlinePlus