Inhibition of Ca<sup>2+</sup>‐sensitive K<sup>+</sup> currents in NG 108‐15 cells by substance P and related tachykinins

Phenna, S.; Carpenter, E.P.; Peers, Chris; Maudsley, Stuart; Gent, J P

doi:10.1111/j.1476-5381.1996.tb15988.x

Cited by 8 publications

(5 citation statements)

References 39 publications

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“…Although other studies have identified inhibitory effects of neurokinins on ion channels in various types of neurons, this is the first report of a neuronal inhibitory action that can be attributed to NK 3 receptors. Substance P was shown to inhibit Ca 2ϩ -dependent K ϩ -channels and other K ϩ channels (Gilbert et al 1998;Otsuka and Yoshioka 1993;Phenna et al 1996); however, the subtype of neurokinin receptor involved was not established. In nucleus basalis cholinergic neurons, substance P inhibits N-but not L-type Ca 2ϩ channel currents (Margeta-Mitrovic et al 1997), but again the type of receptor mediating this effect is not known.…”

Section: Subtypes Of Neurokinin Receptors That Modulate Ca 2ϩ Channelmentioning

confidence: 99%

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca²⁺ Channels in DRG Neurons of the Adult Rat

Sculptoreanu

Groat

2003

Journal of Neurophysiology

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Whole cell patch-clamp techniques were used to examine neurokinin receptor modulation of Ca2+ channels in small to medium size dorsal root ganglia neurons (<40 pF) that express mainly N- and L-type Ca2+ currents. Low concentrations of substance P enhanced Ca2+ currents (5-40%, <0.2 microM), while higher concentrations applied cumulatively reversed these enhancements (5-28% reductions, >0.5 microM). This apparent inhibition by high concentrations of substance P was blocked by the administration of the NK3 antagonist SB 235,375 (0.2 microM). The NK1 agonist, [Sar9,Met11]-substance P (0.05 to 1.0 microM) did not alter Ca2+ currents; whereas the NK2 agonist, [betaAla8]-neurokinin A (4-10), enhanced Ca2+ currents (5-36% increase, 0.05-0.5 microM). The enhancement was reversed by the NK2 antagonist MEN 10,376 (0.2 microM) but unaffected by the NK3 antagonist SB 235,375 (0.2 microM). The NK3 agonist [MePhe7]-neurokinin B (0.5-1.0 microM) inhibited Ca2+ currents (6-24% decrease). This inhibition was not prevented by the NK2 antagonist MEN 10,376 (0.2 microM) but was blocked by the NK3 antagonist SB 235,375 (0.2 microM). Both the enhancement and inhibition of Ca2+ currents by neurokinin agonists were reversed by the protein kinase C inhibitor bisindolylmaleimide I HCl (0.2-0.5 microM). Following inhibition of Ca2+ channels by [MePhe7]-neurokinin the facilitatory effect of BayK 8644 (5 microM) was increased and the inhibitory effect of the N-type Ca2+ channel blocker w -conotoxin GVIA (1 microM) was diminished, suggesting that the NK3 agonist inhibits N-type Ca2+ channels. Similarly, block of all but N-type Ca2+ channels, revealed that [betaAla8]-neurokinin A (4-10) enhanced the currents while [MePhe7]-neurokinin B inhibited the currents. Inhibition of all but L-type Ca2+ channels, revealed that [betaAla8]-neurokinin A (4-10) enhanced the currents while [MePhe7]-neurokinin B had no effect. Activation of protein kinase C with low concentrations of phorbol-12,13-dibutyrate enhanced Ca2+ currents, but high concentrations inhibited N- and L-type Ca2+ currents. In summary, these data suggest that in adult rat dorsal root ganglia neurons, NK2 receptors enhance both L- and N-type Ca2+ channels and NK3 receptors inhibit N-type Ca2+ channels and that these effects are mediated by protein kinase C phosphorylation of Ca2+ channels.

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Section: Subtypes Of Neurokinin Receptors That Modulate Ca 2ϩ Channelmentioning

confidence: 99%

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca²⁺ Channels in DRG Neurons of the Adult Rat

Sculptoreanu

Groat

2003

Journal of Neurophysiology

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“…While the precise mechanism of action mediating NK 3 receptor activity remains unclear, it seems probable that they operate on neonatal rat spinal neurons in a fashion similar to other tachykinin receptors, namely depression of a leak K ϩ conductance (Fisher and Nistri 1993), or of a Ca 2ϩ -dependent K ϩ conductance (Phenna et al 1996), or activation of nonselective cationic channels (Inoue et al 1995). Because intracel-lular recording from QX-314 -injected motoneurons indicated no resistance change during application of senktide, this result suggests that senktide depolarizations were generated either remotely from motoneurons or were due to concurrent activation and depression of motoneuron intrinsic conductances.…”

Section: Distribution and Action Of Nk 3 Receptors In The Rat Spinal mentioning

confidence: 99%

Neuronal Bursting Induced by NK₃ Receptor Activation in the Neonatal Rat Spinal Cord In Vitro

Marchetti

Nistri

2001

Journal of Neurophysiology

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Intracellular recording from lumbar motoneurons and extracellular recording from ventral roots of the neonatal rat isolated spinal cord were used to study the mechanisms responsible for the excitation mediated by NK3 tachykinin receptors. The selective NK3 agonists senktide or [MePhe7]neurokinin B induced a slow depolarization with superimposed oscillations (mean period +/- SD was 2.8 +/- 0.8 s) that, in the majority of cases, showed left-right alternation at segmental level and were synchronous between L2 and L5 of the same side. During agonist wash out (5-20 min) a delayed form of hyperexcitability emerged consisting of bursts lasting 8 +/- 2 s (average interburst interval 55 +/- 21 s) with superimposed oscillations usually with homosegmental alternation and heterosegmental synchronicity. Such bursting was accompanied by depression of GABAergic dorsal root potentials evoked by dorsal root stimulation and of the recurrent inhibitory postsynaptic potential recorded from motoneurons. Despite bursting, motoneuron membrane potential returned to baseline while input resistance was increased. Bursts were a network-dependent phenomenon triggered by previous NK3 receptor activation because bursting was suppressed by glutamate receptor antagonists and was insensitive to motoneuron membrane potential or subsequent application of an NK3 receptor antagonist. NK3 receptors operated synergistically with N-methyl-D-aspartate (NMDA) and 5-hydroxytryptamine (5-HT) to trigger fully alternating locomotor-like rhythms while NK3 receptor antagonism disrupted the same rhythm. In summary, in the neonatal rat spinal cord NK3 receptors could trigger rhythmic activity predominantly with alternation at segmental level but with synchronous coupling between ipsilateral motor pools. NK3 receptor activation could also facilitate fictive locomotor patterns induced by NMDA and 5-HT.

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“…Consistent with our results, the large-conductance I K(Ca) channel has been reported to control the excitability of dentate gyrus (Brenner et al 2005) and transmitter release at CA3-CA3 synapses (Raffaelli et al 2004). More interestingly, I K(Ca) has been shown to be inhibited by a variety of neuropeptides including CCK in CA1 pyramidal neurons (Shinohara & Kawasaki, 1997), neurotensin in acutely dissociated neurons from the diagonal band of Broca (Jassar et al 1999) and in neurons of the solitary tract nucleus (Ogawa et al 2005) and tachykinins in NG 108-15 cells (Phenna et al 1996). Added to this spectrum is our study showing that CCK inhibits I K(Ca) in interneurons where I K(Ca) controls spontaneous firing patterns (Goldberg & Wilson, 2005 While our results demonstrate that the I K(Ca) channel is the major ion channel involved in CCK-mediated modulation of GABA release in the dentate gyrus region, CCK-mediated increases in GABA release in the CA1 region are related to inhibition of a resting K + conductance (Miller et al 1997).…”

Section: Ionic Mechanisms Underlying Cck-mediated Modulation Of Gaba mentioning

confidence: 99%

Bidirectional modulation of GABAergic transmission by cholecystokinin in hippocampal dentate gyrus granule cells of juvenile rats

Deng

Lei

2006

The Journal of Physiology

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A receptor-mediated synaptic transmission in the hippocampal formation and then explored the underlying cellular mechanisms by focusing on the dentate gyrus region, where the highest levels of CCK-binding sites have been detected. Our results indicate that activation of CCK-B receptors initially and transiently increased spontaneous IPSC (sIPSC) frequency, followed by a persistent reduction. The effects of CCK were more evident in juvenile rats, suggesting that they are developmentally regulated. Cholecystokinin failed to modulate the miniature IPSCs recorded in the presence of TTX and the amplitude of the evoked IPSCs, but produced a transient increase followed by a reduction in action potential firing frequency recorded from GABAergic interneurons, suggesting that CCK acts by modulating the excitability of the interneurons to regulate GABA release. Cholecystokinin reduced the amplitude of the after-hyperpolarization of the action potentials, and application of paxilline or charybdotoxin considerably reduced CCK-mediated modulation of sIPSC frequency, suggesting that the effects of CCK are related to the inhibition of Ca 2+ -activated K + currents (I K(Ca) ). The effects of CCK were independent of the functions of phospholipase C, intracellular Ca 2+ release, protein kinase C or phospholipase A 2 , suggesting a direct coupling between the G proteins of CCK-B receptors and I K(Ca) . Our results provide a novel mechanism underlying CCK-mediated modulation of GABA release.

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Inhibition of Ca²⁺‐sensitive K⁺ currents in NG 108‐15 cells by substance P and related tachykinins

Cited by 8 publications

References 39 publications

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca²⁺ Channels in DRG Neurons of the Adult Rat

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca²⁺ Channels in DRG Neurons of the Adult Rat

Neuronal Bursting Induced by NK₃ Receptor Activation in the Neonatal Rat Spinal Cord In Vitro

Bidirectional modulation of GABAergic transmission by cholecystokinin in hippocampal dentate gyrus granule cells of juvenile rats

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Inhibition of Ca2+‐sensitive K+ currents in NG 108‐15 cells by substance P and related tachykinins

Cited by 8 publications

References 39 publications

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca2+ Channels in DRG Neurons of the Adult Rat

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca2+ Channels in DRG Neurons of the Adult Rat

Neuronal Bursting Induced by NK3 Receptor Activation in the Neonatal Rat Spinal Cord In Vitro

Bidirectional modulation of GABAergic transmission by cholecystokinin in hippocampal dentate gyrus granule cells of juvenile rats

Contact Info

Product

Resources

About

Inhibition of Ca²⁺‐sensitive K⁺ currents in NG 108‐15 cells by substance P and related tachykinins

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca²⁺ Channels in DRG Neurons of the Adult Rat

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca²⁺ Channels in DRG Neurons of the Adult Rat

Neuronal Bursting Induced by NK₃ Receptor Activation in the Neonatal Rat Spinal Cord In Vitro