Voltage-dependent effects of opioid peptides on hippocampal CA3 pyramidal neurons in vitro

Moore, SD; Madamba, Samuel G.; Schweitzer, Paul; Siggins, G.R.

doi:10.1523/jneurosci.14-02-00809.1994

Cited by 98 publications

(75 citation statements)

References 58 publications

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“…The SST-induced increase at voltage steps to Ϫ60 mV measured 128 Ϯ 20 pA. This SST effect is similar in magnitude to that reported in rat (Schweitzer et al, 1993;Moore et al, 1994). SST also increased the holding current at Ϫ40 mV by 190 pA.…”

Section: Sst 4 Mediates Sst-induced Increase In I Msupporting

confidence: 85%

Somatostatin Receptor Subtype 4 Couples to the M-Current to Regulate Seizures

Qiu

Zeyda²,

Johnson³

et al. 2008

J. Neurosci.

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The K ϩ M-current (I M , Kv7) is an important regulator of cortical excitability, and mutations in these channels cause a seizure disorder in humans. The neuropeptide somatostatin (SST), which has antiepileptic properties, augments I M in hippocampal CA1 pyramidal neurons. We used SST receptor knock-out mice and subtype-selective ligands to investigate the receptor subtype that couples to I M and mediates the antiepileptic effects of SST. Using pentylenetetrazole as a chemoconvulsant, SST 2 , SST 3 , and SST 4 receptor knock-out mice all had shorter latencies to different seizure stages and increased seizure severity when compared with wild-type mice. However, the most robust differences were observed in the SST 4 knock-outs. When seizures were induced by systemic injection of kainate, only SST 4 knock-outs showed an increase in seizure sensitivity. We next examined the action of SST and subtype-selective SST agonists on electrophysiological parameters in hippocampal slices of wild-type and receptor knock-out mice. SST 2 and SST 4 appear to mediate the majority of SST inhibition of epileptiform activity in CA1. SST lacked presynaptic effects in mouse CA1, in contrast to our previous findings in rat. SST increased I M in CA1 pyramidal neurons of wild-type and SST 2 knock-out mice, but not SST 4 knock-out mice. Using M-channel blockers, we found that SST 4 coupling to M-channels is critical to its inhibition of epileptiform activity. This is the first demonstration of an endogenous enhancer of I M that is important in controlling seizure activity. SST 4 receptors could therefore be an important novel target for developing new antiepileptic and antiepileptogenic drugs.

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Section: Sst 4 Mediates Sst-induced Increase In I Msupporting

confidence: 85%

Somatostatin Receptor Subtype 4 Couples to the M-Current to Regulate Seizures

Qiu

Zeyda²,

Johnson³

et al. 2008

J. Neurosci.

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“…Selective κ receptor agonists (e.g., U50,488H) attenuate both the release of glutamate and increases in [Ca 2+ ] i in synaptosomes in response to K + -induced membrane depolarization (24,25 (31). In addition, dynorphin A recently has been shown to hyperpolarize membrane potential by decreasing voltage-dependent K + currents (K M currents) (61). Dynorphin A similarly reduces the sensitivity of dorsal horn neurons to excitatory amino acids through modulation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors (43).…”

Section: Discussionmentioning

confidence: 99%

Dynorphin A (1–13) Neurotoxicity in Vitro: Opioid and Non-Opioid Mechanisms in Mouse Spinal Cord Neurons

Hauser

Foldes

Turbek

1999

Experimental Neurology

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Dynorphin A is an endogenous opioid peptide that preferentially activates κ opioid receptors and is antinociceptive at physiological concentrations. Levels of dynorphin A and a major metabolite, dynorphin A (1-13), increase significantly following spinal cord trauma and reportedly contribute to neurodegeneration associated with secondary injury. Interestingly, both κ opioid and N-methyl-D-aspartate (NMDA) receptor antagonists can modulate dynorphin toxicity, suggesting that dynorphin is acting (directly or indirectly) through κ opioid and/or NMDA receptor (NMDAR) types. Despite these findings, few studies have systematically explored dynorphin toxicity at the cellular level in defined populations of neurons co-expressing κ opioid and NMDA receptors. To address this question, we isolated populations of neurons enriched in both κ opioid and NMDA receptors from embryonic mouse spinal cord and examined the effects of dynorphin A (1-13) on intracellular calcium concentration ([Ca 2+ ] i ) and neuronal survival in vitro. Time-lapse photography was used to repeatedly follow the same neurons before and during experimental treatments. At micromolar concentrations, dynorphin A (1-13) elevated [Ca 2+ ] i and caused a significant loss of neurons. The excitotoxic effects were prevented by MK-801 (Dizocilpine) (10 μM), 2-amino-5-phosphopentanoic acid (AP-5) (100 μM), or 7-chlorokynurenic acid (100 μM)-suggesting that dynorphin A (1-13) was acting (directly or indirectly) through NMDA receptors. In contrast, co-treatment with (−)-naloxone (3 μM), or the more selective κ opioid receptor antagonist nor-binaltorphimine (3 μM), exacerbated dynorphin A (1-13)-induced neuronal loss; however, cell losses were not enhanced by the inactive stereoisomer (+)-naloxone (3 μM). Neuronal losses were not seen with exposure to the opioid antagonists alone (10 μM). Thus, opioid receptor blockade significantly increased toxicity, but only in the presence of excitotoxic levels of dynorphin. This provided indirect evidence that dynorphin also stimulates κ opioid receptors and suggests that κ receptor activation may be moderately neuroprotective in the presence of an excitotoxic insult. Our findings suggest that dynorphin A (1-13) can have paradoxical effects on neuronal viability through both opioid and non-opioid (glutamatergic) receptor-mediated actions. Therefore, dynorphin A potentially modulates secondary neurodegeneration in the spinal cord through complex interactions involving multiple receptors and signaling pathways.

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“…G-protein-coupled receptor agonists capable of modulating the M-current include muscarinic (M 1 /M 3 ) Constanti and Brown, 1981;Halliwell and Adams, 1982), substance P (Jones, 1985), luteinizing hormone releasing hormone , purinergic (P2Y) , ␤-adrenergic (Akasu, 1988), angiotensin II (AT 1 ) (Shapiro et al, 1994;Zaika et al, 2006), serotonin (5-hydroxytryptamine-2) (Colino and Halliwell, 1987), opiates ( and ␦) (Moore et al, 1994), and glutamate (metabotropic glutamate receptors 1/5) (Charpak et al, 1990). It is interesting that agonists such as angiotensin II and serotonin are also hormones that play a significant role in cardiovascular homeostasis through direct actions on vascular smooth muscle cells.…”

Section: Historical Perspectivementioning

confidence: 99%