Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells.

Tsunoo, Akinobu; Yoshii, Mitsunobu; Narahashi, Toshio

doi:10.1073/pnas.83.24.9832

Cited by 178 publications

(111 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In many cell types, G protein-mediated effects on the Ca 2ϩ current can be reversed by brief depolarizing prepulses, leading to prepulse facilitation (19)(20)(21). This reversal of G protein modulation is thought to reflect a shift of Ca 2ϩ channels from the R to the W state induced by strong depolarization (16).…”

Section: G Protein Modulationmentioning

confidence: 99%

“…This inhibition can be reversed by strong depolarization leading to prepulse facilitation of Ca 2ϩ currents (19)(20)(21)(22). The effect of G proteins has been modeled as a shift in channel state from a ''willing'' (W) state, in which activation occurs rapidly at relatively negative membrane potentials, to a ''reluctant'' (R) state, in which activation is slower and requires stronger depolarization (16).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Allosteric modulation of Ca ²⁺ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Ca _v β subunits

Herlitze

Zhong

Scheuer

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

N-type and P͞Q-type Ca 2؉ channels are inhibited by neurotransmitters acting through G protein-coupled receptors in a membranedelimited pathway involving G␤␥ subunits. Inhibition is caused by a shift from an easily activated ''willing'' (W) state to a moredifficult-to-activate ''reluctant'' (R) state. This inhibition can be reversed by strong depolarization, resulting in prepulse facilitation, or by protein kinase C (PKC) phosphorylation. Comparison of regulation of N-type Ca 2؉ channels containing Cav2.2a ␣1 subunits and P͞Q-type Ca 2؉ channels containing Cav2.1 ␣1 subunits revealed substantial differences. In the absence of G protein modulation, Ca v 2.1 channels containing Ca v ␤ subunits were tonically in the W state, whereas Cav2.1 channels without ␤ subunits and Cav2.2a channels with ␤ subunits were tonically in the R state. Both Cav2.1 and Ca v2.2a channels could be shifted back toward the W state by strong depolarization or PKC phosphorylation. Our results show that the R state and its modulation by prepulse facilitation, PKC phosphorylation, and Ca v␤ subunits are intrinsic properties of the Ca 2؉ channel itself in the absence of G protein modulation. A common allosteric model of G protein modulation of Ca 2؉ -channel activity incorporating an intrinsic equilibrium between the W and R states of the ␣1 subunits and modulation of that equilibrium by G proteins, Ca v␤ subunits, membrane depolarization, and phosphorylation by PKC accommodates our findings. Such regulation will modulate transmission at synapses that use N-type and P͞Q-type Ca 2؉ channels to initiate neurotransmitter release.neuromodulation ͉ calcium channels ͉ G␤␥ subunits ͉ protein phosphorylation N euronal voltage-gated Ca 2ϩ channels are involved in multiple cellular functions including neurotranstransmitter release, Ca 2ϩ -mediated regulatory processes, and generation of dendritic action potentials. Electrophysiological and pharmacological studies distinguish at least six classes of Ca 2ϩ currents designated L-, N-, P-, Q-, R-, and T-type (1, 2). Ca 2ϩ channels consist of complexes of a pore-forming ␣ 1 subunit with ␣ 2

show abstract

Section: G Protein Modulationmentioning

confidence: 99%

mentioning

confidence: 99%

Allosteric modulation of Ca ²⁺ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Ca _v β subunits

Herlitze

Zhong

Scheuer

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Binding of G proteins is thought to cause a shift of gating mode from an easily activated ''willing'' (W) state to a ''reluctant'' (R) state (24). Strong depolarization shifts the channels back from the R state to the W state, producing prepulse facilitation (9,25,26).…”

mentioning

confidence: 99%

Control of gating mode by a single amino acid residue in transmembrane segment IS3 of the N-type Ca ²⁺ channel

Zhong

Scheuer

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

N-type Ca 2؉ channels can be inhibited by neurotransmitter-induced release of G protein ␤␥ subunits. Two isoforms of Cav2.2 ␣1 subunits of N-type calcium channels from rat brain (Ca v2.2a and Cav2.2b; initially termed rbB-I and rbB-II) have different functional properties. Unmodulated Ca v2.2b channels are in an easily activated ''willing'' (W) state with fast activation kinetics and no prepulse facilitation. Activating G proteins shifts Cav2.2b channels to a difficult to activate ''reluctant'' (R) state with slow activation kinetics; they can be returned to the W state by strong depolarization resulting in prepulse facilitation. This contrasts with Ca v 2.2a channels, which are tonically in the R state and exhibit strong prepulse facilitation. Activating or inhibiting G proteins has no effect. Thus, the R state of Cav2.2a and its reversal by prepulse facilitation are intrinsic to the channel and independent of G protein modulation. Mutating G177 in segment IS3 of Ca v2.2b to E as in Ca v2.2a converts Cav2.2b tonically to the R state, insensitive to further G protein modulation. The converse substitution in Cav2.2a, E177G, converts it to the W state and restores G protein modulation. We propose that negatively charged E177 in IS3 interacts with a positive charge in the IS4 voltage sensor when the channel is closed and produces the R state of Ca v2.2a by a voltage sensor-trapping mechanism. G protein ␤␥ subunits may produce reluctant channels by a similar molecular mechanism.neuromodulation ͉ G protein ͉ voltage sensor ͉ facilitation

show abstract

“…26,54 It is known that enkephalin directly inhibits neurotransmitter release, including substance P, from presynaptic nerve terminals in both the central and peripheral nervous systems, 55 through a calcium channel blocking action. 56 Thus, met-enkephalin is capable of directly reducing pain-related neurotransmitter release and reducing inflammation through these mechanisms. The month-long duration of the antihyperalgesic effect and the profound tissue preservation seen after a single administration in these studies implies that infusions of viral vectors directly into the pancreas and other sites may provide prolonged site-specific relief from chronic pain and tissue protection from inflammatory responses for patients with use of clinically approved vectors.…”

Section: Anti-inflammatory Effects and Tissue Protection By Hsv-enk Tmentioning

confidence: 99%

Gene therapy for pancreatitis pain

Westlund

2009

Gene Ther

View full text Add to dashboard Cite

Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells.

Abstract: Leucine-enkephalin, methionine-enkephalin, and morphine caused a reversible block of Ca21 channel currents in neuroblastoma-glioma hybrid cells (NG108-15

Cited by 178 publications

References 36 publications

Allosteric modulation of Ca ²⁺ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Ca _v β subunits

Allosteric modulation of Ca ²⁺ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Ca _v β subunits

Control of gating mode by a single amino acid residue in transmembrane segment IS3 of the N-type Ca ²⁺ channel

Gene therapy for pancreatitis pain

Contact Info

Product

Resources

About

Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells.

Abstract: Leucine-enkephalin, methionine-enkephalin, and morphine caused a reversible block of Ca21 channel currents in neuroblastoma-glioma hybrid cells (NG108-15

Cited by 178 publications

References 36 publications

Allosteric modulation of Ca 2+ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Ca v β subunits

Allosteric modulation of Ca 2+ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Ca v β subunits

Control of gating mode by a single amino acid residue in transmembrane segment IS3 of the N-type Ca 2+ channel

Gene therapy for pancreatitis pain

Contact Info

Product

Resources

About

Allosteric modulation of Ca ²⁺ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Ca _v β subunits

Allosteric modulation of Ca ²⁺ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Ca _v β subunits

Control of gating mode by a single amino acid residue in transmembrane segment IS3 of the N-type Ca ²⁺ channel