T-type calcium channel regulation by specific G-protein βγ subunits

  title={T-type calcium channel regulation by specific G-protein $\beta$$\gamma$ subunits},
  author={Joshua T. Wolfe and Hongge Wang and Jason Howard and James C. Garrison and Paula Q. Barrett},
Low-voltage-activated (LVA) T-type calcium channels have a wide tissue distribution and have well-documented roles in the control of action potential burst generation and hormone secretion. In neurons of the central nervous system and secretory cells of the adrenal and pituitary, LVA channels are inhibited by activation of G-protein-coupled receptors that generate membrane-delimited signals, yet these signals have not been identified. Here we show that the inhibition of α1H (Cav3.2), but not… 

G Protein Modulation of Voltage-Gated Calcium Channels

Evidence suggests a key role for the β subunits of calcium channels in the process of Gprotein modulation, and the role of a class of proteins termed “regulators of G protein signaling” will also be described.

A Mechanism for the Direct Regulation of T-Type Calcium Channels by Ca2+/Calmodulin-Dependent Kinase II

The α1H channel is identified as a new substrate for CaMKII and the first molecular mechanism for the direct regulation of T-type Ca2+ channels by a protein kinase is provided, suggesting a novel mechanism for modulating the integrative properties of neurons.

The molecular basis for T-type Ca2+ channel inhibition by G protein β2γ2 subunits

This work used pure recombinant Gβγ subunits to establish that the Gβ2γ2 dimer can selectively reconstitute the inhibition of α1H channels in isolated membrane patches and identified a cluster of amino acids that functionally distinguish G β2 from other Gβ subunits.

G protein inhibition of CaV2 calcium channels

This article will review the basics of Ca2+-channels and G protein signaling, and the functional impact of this now classical inhibitory mechanism on channel function, and provide an update on more recent developments in the field.

Protein Kinase A Activity Controls the Regulation of T-type CaV3.2 Channels by Gβγ Dimers*

It is proposed that a dual-receptor regulatory mechanism is used by dopamine to control Cav3.2 channel activity, which would be important in aldosterone producing adrenal glomerulosa cells where channel dysregulation would lead to overproduction of ald testosterone and consequent cardiac, renal, and brain target organ damage.

Regulation of T-type calcium channels by Rho-associated kinase

ROCK activation by LPA reduced native T-type currents in Y79 retinoblastoma and in lateral habenular neurons, and upregulated native Cav3.2 current in dorsal root ganglion neurons, suggesting that ROCK is an important regulator of T- type calcium channels, with potentially far-reaching implications for multiple cell functions modulated by L PA.

Protein Kinase C-Mediated Inhibition of Recombinant T-Type CaV3.2 Channels by Neurokinin 1 Receptors

It is demonstrated that recombinant CaV3.2 channels are reversibly inhibited by NK1 receptors when both proteins are transiently coexpressed in human embryonic kidney 293 cells, providing novel evidence regarding the mechanisms underlying T-type calcium channel modulation by G protein-coupled receptors.

Direct G Protein Modulation of Cav2 Calcium Channels

Twenty-five years after this mode of physiological regulation was first described, the investigations that have led to the current understanding of its molecular mechanisms are reviewed.

Molecular Regulation of Voltage-Gated Ca2+ Channels

  • R. Felix
  • Biology
    Journal of receptor and signal transduction research
  • 2005
Recent advances that have provided important clues to the underlying molecular mechanisms involved in the regulation of CaV channels by protein phosphorylation, G-protein activation, and interactions with Ca2 +-binding and SNARE proteins are summarized.

Augmentation of Cav3.2 T-Type Calcium Channel Activity by cAMP-Dependent Protein Kinase A

Using chimeric channels constructed by replacing individual cytoplasmic loops of Cav3.2 with those of the Nav1.4 channel, which is insensitive to PKA, a region required for the PKA-mediated augmentation to the II-III loop of the Cav 3.2 channels was localized.



Voltage-dependent modulation of N-type calcium channels by G-protein β γsubunits

It is shown that transient overexpression of Gβγ in sympathetic neurons mimics and occludes the voltage-dependent Ca2+ channel modulation produced by noradrenaline (NA), and indicates that it is G βγ, and not Gα, that mediates voltage- dependent inhibition of N-type Ca 2+ channels.

Modulation of Ca2+ channels βγ G-protein py subunits

It is reported that Gβγ subunits can modulate Ca2+ channels and that overexpression of exogenous Gβ subunits is sufficient to cause channel modulation.

Direct binding of G-protein βλ complex to voltage-dependent calcium channels

Mutation of an arginine residue within the N-terminal motif abolished βλ binding and rendered the channel refractory to G-protein modulation when expressed in Xenopus oocytes, showing that the interaction is indeed responsible for G- protein-dependent modulation of Ca2+ channel activity.

Structure and regulation of voltage-gated Ca2+ channels.

  • W. Catterall
  • Biology
    Annual review of cell and developmental biology
  • 2000
The distinct structures and patterns of regulation of these three families of Ca(2+) channels provide a flexible array of Ca('s 2+) entry pathways in response to changes in membrane potential and a range of possibilities for regulation of Ca (2+) entry by second messenger pathways and interacting proteins.

Crosstalk between G proteins and protein kinase C mediated by the calcium channel α1 subunit

Crosstalk results from the PKC-dependent phosphorylation of one of the Gβλ binding sites which antagonizes G βλ-induced inhibition, providing a mechanism for the highly regulated and dynamic control of neurotransmitter release that depends on the integration of multiple presynaptic signals.

Molecular physiology of low-voltage-activated t-type calcium channels.

The goal of this review is to provide a comprehensive description of T-type currents, their distribution, regulation, pharmacology, and cloning.

Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem

It is reported here that the GTP-bound form of kir/Gem, identified originally as a Ras-related small G-protein that binds CaM, inhibits high-voltage-activated Ca2+ channel activities by interacting directly with the β-subunit.

Functional Properties of CaV1.3 (α1D) L-type Ca2+ Channel Splice Variants Expressed by Rat Brain and Neuroendocrine GH3 Cells*

It is demonstrated that alternatively spliced α1Dtranscripts form functional Ca2+ channels that exhibit voltage-dependent, G protein-independent facilitation and the QXXER motif, located on the C terminus ofα1D-S subunit, is not sufficient to confer sensitivity to inhibitory G proteins.

Activation and inhibition of G protein-coupled inwardly rectifying potassium (Kir3) channels by G protein βγ subunits

It is found that β5γ2 could bind to the same GIRK channel cytoplasmic domains as other, activating Gβγ subunits, and β5-containing dimers inhibit G βγ-stimulated GIRk channels, perhaps by directly binding to the channels.