Ca2+ and Phosphatidylinositol 4,5-Bisphosphate Stabilize a Gβγ-sensitive State of CaV2 Ca2+ Channels*

Direct interactions between G-protein βγ subunits and N- or P/Q-type Ca2+ channels mediate the inhibitory action of several neurotransmitters in the brain. Membrane potential, channel phosphorylation, or auxiliary subunit association tightly regulate these interactions and the consequent inhibition of Ca2+ current. We now provide evidence that intracellular Ca2+ concentration and phosphoinositides play a stabilizing role in this direct voltage-dependent inhibition. Lowering resting cytosolic Ca2+ concentration in Xenopus oocytes expressing CaV2Ca2+ channels strongly decreased basal as well as phasic, agonist-dependent inhibition of Ca2+ channels by G-proteins. Decreasing phosphoinositide levels also suppressed G-protein inhibition and completely occluded the effects of a subsequent injection of Ca2+ chelator. Similar regulations are observed in mouse dorsal root ganglia neurons. Alteration of G-protein block by these agents is independent of protein phosphorylation, cytoskeleton dynamics, and GTPase or GDP/GTP exchange activity, suggesting a direct action at the level of the Ca2+ channel/Gβγ-protein interaction. Moreover, affinity binding experiments of intracellular loops of the CaV2.1 Ca2+ channels to different phospholipids revealed specific interactions between the C-terminal tail of the channel and phosphoinositides. Taken together these data indicate that a Ca2+-sensitive interaction of the C-terminal tail of P/Q channels with the plasma membrane is important for G-protein regulation.

• Publication year

  2004

• Venue

  Journal of Biological Chemistry

• Publication date

  2004-04-09

• Fields of study

  Biology, Chemistry

• Identifiers
  DOI 10.1074/JBC.M313284200
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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