G-protein-independent modulation of P-type calcium channels by μ-opioids in Purkinje neurons of rat

Iegorova, Olena; Fisyunov, Alexander; Krishtal, O. A.

doi:10.1016/j.neulet.2010.06.015

Cited by 19 publications

(22 citation statements)

References 18 publications

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“…In addition to blocking PPN oscillations with GDP-β-S, we measured the frequency of PPN oscillations by activating G-proteins with GTP-γ-S (0.4 mM). This agent is known to reversibly activate G-proteins (31, 32). We used an extracellular solution containing SB, TTX, MEC, PIR, and CAR.…”

Section: Resultsmentioning

confidence: 99%

Muscarinic Modulation of High Frequency Oscillations in Pedunculopontine Neurons

et al. 2013

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We previously reported that persistent application of the non-specific cholinergic agonist carbachol (CAR) increased the frequency of calcium channel-mediated oscillatory activity in pedunculopontine nucleus (PPN) neurons, which we identified as dependent on voltage-gated, high-threshold P/Q-type channels. Here, we tested the hypothesis that M2 muscarinic receptors and G-proteins associated with M2 receptors mediate the increase in oscillatory frequency in PPN neurons. We found, using depolarizing ramps, that patch clamped 9–12 day old rat PPN neurons (n = 189) reached their peak oscillatory activity around −20 mV membrane potential. Acute (short duration) application of CAR blocked the oscillatory activity through M2 muscarinic receptors, an effect blocked by atropine. However, persistent (long duration) application of CAR significantly increased the frequency of oscillatory activity in PPN neurons through M2 receptors [40 ± 1 Hz (with CAR) vs. 23 ± 1 Hz (without CAR); p < 0.001]. We then tested the effects of the G-protein antagonist guanosine 5′-[β-thio] diphosphate trilithium salt (GDP-β-S), and the G-protein agonist 5′-[γ-thio] triphosphate trilithium salt (GTP-γ-S). We found, using a three-step protocol in voltage-clamp mode, that the increase in the frequency of oscillations induced by M2 cholinergic receptors was linked to a voltage-dependent G-protein mechanism. In summary, these results suggest that persistent cholinergic input creates a permissive activation state in the PPN that allows high frequency P/Q-type calcium channel-mediated gamma oscillations to occur.

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Section: Resultsmentioning

confidence: 99%

Muscarinic Modulation of High Frequency Oscillations in Pedunculopontine Neurons

et al. 2013

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“…In contrast, some studies show that opioid receptor activation activates Ca 2+ channels. For example, the MOR agonist DAMGO (10 nM) produces a small yet consistent facilitation of Ca 2+ current through P-type calcium channels via G-protein-independent mechanism in the rat Purkinje neurons [127]. The opioid-induced elevation of intracellular Ca 2+ could explain the excitatory effect of opioids on some presynaptic neurons and consequent regulation of neuro-transmitter release [128, 129].…”

Section: Advances In Research On Opioid Receptor Functionsmentioning

confidence: 99%

Current Research on Opioid Receptor Function

Feng

He²,

Yang³

et al. 2012

CDT

287

186

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The use of opioid analgesics has a long history in clinical settings, although the comprehensive action of opioid receptors is still less understood. Nonetheless, recent studies have generated fresh insights into opioid receptor-mediated functions and their underlying mechanisms. Three major opioid receptors (μ-opioid receptor, MOR; δ-opioid receptor, DOR; and κ-opioid receptor, KOR) have been cloned in many species. Each opioid receptor is functionally sub-classified into several pharmacological subtypes, although, specific gene corresponding each of these receptor subtypes is still unidentified as only a single gene has been isolated for each opioid receptor. In addition to pain modulation and addiction, opioid receptors are widely involved in various physiological and pathophysiological activities, including the regulation of membrane ionic homeostasis, cell proliferation, emotional response, epileptic seizures, immune function, feeding, obesity, respiratory and cardiovascular control as well as some neurodegenerative disorders. In some species, they play an essential role in hibernation. One of the most exciting findings of the past decade is the opioid-receptor, especially DOR, mediated neuroprotection and cardioprotection. The up-regulation of DOR expression and DOR activation increase the neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers (depending on stress duration and severity) different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of homeostasis and increased pro-survival signaling (e.g., PKC-ERK-Bcl 2) and anti-oxidative capacity. In the heart, PKC and KATP channels are involved in the opioid receptor-mediated cardioprotection. The DOR-mediated neuroprotection and cardioprotection have the potential to significantly alter the clinical pharmacology in terms of prevention and treatment of life-threatening conditions like stroke and myocardial infarction. The main purpose of this article is to review the recent work done on opioids and their receptor functions. It shall provide an informative reference for better understanding the opioid system and further elucidation of the opioid receptor function from a physiological and pharmacological point of view.

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“…Endogenous opioids have very diverse roles in many different tissues. For example, opioids typically have an inhibitory effect on neuronal activity, but the μ-opioid receptor agonist DAMGO (Tyr- d -Ala-Gly- N -methyl-Phe-Gly-ol) is able to regulate resting membrane potential in Purkinje neurons by its ability to increase intracellular calcium levels via a G protein-independent pathway, which results in increased neurotransmitter release (Iegorova, Fisyunov, & Krishtal, 2010). Painful stimuli including injuries and lipopolysaccharide administration are known to cause an upregulation of the μ-opioid receptor agonist β endorphin, which serves as a natural form of analgesia (Molina, 2002), and opioids are able to control feeding depending on which receptor subtype is bound (Gosnell & Levine, 2009).…”

Section: Opioid System Overviewmentioning

confidence: 99%

Functions of the Chemokine Receptor CXCR4 in the Central Nervous System and Its Regulation by μ-Opioid Receptors

Nash

Meucci

2014

International Review of Neurobiology

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Activation of the G protein-coupled receptor CXCR4 by its chemokine ligand CXCL12 regulates a number of physiopathological functions in the central nervous system, during development as well as later in life. In addition to the more classical roles of the CXCL12/CXCR4 axis in the recruitment of immune cells or migration and proliferation of neural precursor cells, recent studies suggest that CXCR4 signaling also modulates synaptic function and neuronal survival in the mature brain, through direct and indirect effects on neurons and glia. These effects, which include regulation of glutamate receptors and uptake, and of dendritic spine density, can significantly alter the ability of neurons to face excitotoxic insults. Therefore, they are particularly relevant to neurodegenerative diseases featuring alterations of glutamate neurotransmission, such as HIV-associated neurocognitive disorders. Importantly, CXCR4 signaling can be dysregulated by HIV viral proteins, host HIV-induced factors, and opioids. Potential mechanisms of opioid regulation of CXCR4 include heterologous desensitization, transcriptional regulation and changes in receptor expression levels, opioid–chemokine receptor dimer or heteromer formation, and the newly described modulation by the protein ferritin heavy chain—all leading to inhibition of CXCR4 signaling. After reviewing major effects of chemokines and opioids in the CNS, this chapter discusses chemokine–opioid interactions in neuronal and immune cells, focusing on their potential contribution to HIV-associated neurocognitive disorders.

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G-protein-independent modulation of P-type calcium channels by μ-opioids in Purkinje neurons of rat

Cited by 19 publications

References 18 publications

Muscarinic Modulation of High Frequency Oscillations in Pedunculopontine Neurons

Muscarinic Modulation of High Frequency Oscillations in Pedunculopontine Neurons

Current Research on Opioid Receptor Function

Functions of the Chemokine Receptor CXCR4 in the Central Nervous System and Its Regulation by μ-Opioid Receptors

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