Neil Marrion - Academia.edu (original) (raw)

Papers by Neil Marrion

Church TW, Brown JT, Marrion NV. 3-Adrenergic receptordependent modulation of the medium afterhyp... more Church TW, Brown JT, Marrion NV. 3-Adrenergic receptordependent modulation of the medium afterhyperpolarization in rat hippocampal CA1 pyramidal neurons. J Neurophysiol 121: 773–784, 2019. First published January 9, 2019; doi:10.1152/jn.00334.2018.— Action potential firing in hippocampal pyramidal neurons is regulated by generation of an afterhyperpolarization (AHP). Three phases of AHP are recognized, with the fast AHP regulating action potential firing at the onset of a burst and the medium and slow AHPs supressing action potential firing over hundreds of milliseconds and seconds, respectively. Activation of -adrenergic receptors suppresses the slow AHP by a protein kinase A-dependent pathway. However, little is known regarding modulation of the medium AHP. Application of the selective -adrenergic receptor agonist isoproterenol suppressed both the medium and slow AHPs evoked in rat CA1 hippocampal pyramidal neurons recorded from slices maintained in organotypic culture. Suppressio...

Changes in extracellular pH occur during both physiological neuronal activity and pathological co... more Changes in extracellular pH occur during both physiological neuronal activity and pathological conditions such as epilepsy and stroke. Such pH changes are known to exert profound effects on neuronal activity and survival. Heteromeric KCNQ2/3 potassium channels constitute a potential target for modulation by H ions as they are expressed widely within the CNS and have been proposed to underlie the M-current, an important determinant of excitability in neuronal cells. Whole-cell and single-channel recordings demonstrated a modulation of heterologously expressed KCNQ2/3 channels by extracellular H ions. KCNQ2/3 current was inhibited by H ions with an IC 50 of 52 nM (pH 7.3) at 60 mV, rising to 2 M (pH 5.7) at 10 mV. Neuronal M-current exhibited a similar sensitivity. Extracellular H ions affected two distinct properties of KCNQ2/3 current: the maximum current attainable upon depolarization (I max ) and the voltage dependence of steady-state activation. Reduction of I max was antagonized...

Molecular Pharmacology

Three small conductance calcium-activated potassium channel (SK) subunits have been cloned and fo... more Three small conductance calcium-activated potassium channel (SK) subunits have been cloned and found to preferentially form heteromeric channels when expressed in a heterologous expression system. The original cloning of the gene encoding the intermediate conductance calcium-activated potassium channel (IKCa) was termed SK4 because of the high homology between channel subtypes. Recent immunovisualization suggests that IKCa is expressed in the same subcellular compartments of some neurons as SK channel subunits. Stochastic optical reconstruction microscopy super-resolution microscopy revealed that coexpressed IKCa and SK1 channel subunits were closely associated, a finding substantiated by measurement of fluorescence resonance energy transfer between coexpressed fluorophore-tagged subunits. Expression of homomeric SK1 channels produced current that displayed typical sensitivity to SK channel inhibitors, while expressed IKCa channel current was inhibited by known IKCa channel blockers. Expression of both SK1 and IKCa subunits gave a current that displayed no sensitivity to SK channel inhibitors and a decreased sensitivity to IKCa current inhibitors. Single channel recording indicated that coexpression of SK1 and IKCa subunits produced channels with properties intermediate between those observed for homomeric channels. These data indicate that SK1 and IKCa channel subunits preferentially combine to form heteromeric channels that display pharmacological and biophysical properties distinct from those seen with homomeric channels.

Frontiers in Synaptic …, 2010

Glutamate is released from synaptic vesicles following formation of a fusion pore, connecting the... more Glutamate is released from synaptic vesicles following formation of a fusion pore, connecting the vesicle interior with the synaptic cleft. Release is proposed to result from either full fusion of the vesicle with the terminal membrane or by ‘kiss-and-run,’ where release occurs through the fusion pore. ‘Kiss-and-run’ seems implausible as passive diffusion of glutamate through the pore is too slow to account for the rapidity of release. Vesicular accumulation of glutamate is driven by a proton gradient, resulting in the co-release of protons during exocytosis. We tested whether the proton gradient between the vesicle and cleft contributes to glutamate exocytosis. Collapse of the gradient reduced hippocampal glutamatergic transmission, an effect that was not associated with presynaptic changes in excitability, transmitter release probability, or postsynaptic sensitivity. These data indicate that approximately half of glutamate release utilizes the proton gradient between vesicle and cleft, suggesting a significant proportion of release by ‘kiss-and-run.’

The Journal of Neuroscience

L-type calcium channels are abundant in hippocampal pyramidal neurons and are highly clustered at... more L-type calcium channels are abundant in hippocampal pyramidal neurons and are highly clustered at the base of the major dendrites. However, little is known of their function in these neurons. Single-channel recording using a low concentration of permeant ion reveals a long-lasting facilitation of L-type channel activity that is induced by a depolarizing prepulse or a train of action potential waveforms. This facilitation exhibits a slow rise, peaking 0.5-1 sec after the train and decaying over several seconds. We have termed this behavior "delayed facilitation," because of the slow onset. Delayed facilitation results from an increase in opening frequency and the recruitment of longer duration openings. This behavior is observed at all membrane potentials between Ϫ20 and Ϫ60 mV, with the induction and magnitude of facilitation being insensitive to voltage. ␤-Adrenergic receptor activation blocks induction of delayed facilitation but does not significantly affect normal L-type channel activity. Delayed facilitation of L-type calcium channels provides a prolonged source of calcium entry at negative membrane potentials. This behavior may underlie calciumdependent events that are inhibited by ␤-adrenergic receptor activation, such as the slow afterhyperpolarization in hippocampal neurons.

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13880/full. Nuclear hormone receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, catalytic receptors, enzym...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13877/full. Enzymes are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic recepto...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13883/full. Transporters are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic re...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13876/full. Catalytic receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, enzym...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 is the third in this series of biennial publications. T... more The Concise Guide to PHARMACOLOGY 2017/18 is the third in this series of biennial publications. This version provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13882/full. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are eight areas of focus: G protein-coupled recepto...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13879/full. Ligand-gated ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzym...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13881/full. Other ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, nuclear hormone receptors, catalytic receptors, enzym...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13878/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzym...

Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for NeuroReport. Ente... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for NeuroReport. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining ...

Brain Research, May 30, 2007

The firing of a train of action potentials in hippocampal pyramidal neurons is terminated by an a... more The firing of a train of action potentials in hippocampal pyramidal neurons is terminated by an afterhyperpolarization (AHP) that displays two main components; the medium AHP (I(mAHP)), lasting a few hundred milliseconds and the slow AHP (I(sAHP)), that has a duration of several seconds. It is unclear how much of I(mAHP) is dependent on the entry of calcium ions (Ca(2+)), whereas it is accepted that I(sAHP) is caused by activation of Ca(2+)-activated potassium channels. There has been controversy regarding the subcellular localization and mechanism of activation of these channels. Whole-cell recordings from CA1 neurons in the hippocampal slice preparation showed that inhibition of L-type, but not N-, P/Q-, T- and R-type Ca(2+) channels, reduced both I(mAHP) and I(sAHP). Inhibition of both AHP components by L-type Ca(2+) channel antagonists was not complete, with I(sAHP) being significantly more sensitive than I(mAHP). Somatic extracellular ionophoresis of BAPTA during I(sAHP) caused a transient inhibition, but had no effect on I(mAHP). Cell-attached patch recordings from the soma of CA1 neurons within a slice displayed channels that produced an ensemble waveform reminiscent of I(sAHP) when the patch was subjected to a train of action potential waveforms. The channels were Ca(2+)-activated, exhibited a limiting slope conductance of 19 pS and were not observed in dendritic membrane patches. These data demonstrate that the I(sAHP) is somatic in origin and arises from continued Ca(2+) entry through functionally co-localized L-type channels.

Expert opinion on therapeutic targets, Jan 26, 2016

Atrial fibrillation (AF) is the most common arrhythmia in humans. It is progressive and the devel... more Atrial fibrillation (AF) is the most common arrhythmia in humans. It is progressive and the development of electrical and structural remodelling makes early intervention desirable. Existing antiarrhythmic pharmacological approaches are not always effective and can produce unwanted side effects. Additional atrial-selective antiarrhythmic strategies are therefore desirable. Areas covered: Evidence for three novel ion channel atrial-selective therapeutic targets is evaluated: atrial-selective fast sodium channel current (INa) inhibition; small conductance calcium-activated potassium (SK) channels; and two-pore (K2P) potassium channels. Expert Opinion: Data from animal models support atrial-ventricular differences in INa kinetics and also suggests atrial-ventricular differences in sodium channel β subunit expression. Further work is required to determine whether intrinsic atrial-ventricular differences in human INa exist or whether functional differences occur due to distinct atrial and...

Neuroreport, 2008

There is confusion in the literature concerning the relative agonist efficacy of methadone at mic... more There is confusion in the literature concerning the relative agonist efficacy of methadone at micro-opioid receptors (MOPrs). Here, we confirm that methadone is a full agonist in guanosine 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-O-[gamma-thio]triphosphate (GTPgammaS) binding studies. Methadone, however, seems to have low efficacy in studies of MOPr activation of G-protein-gated potassium (GIRK) channels, but this is because it directly inhibits the GIRK channels. Methadone also inhibits alpha2-adrenoceptor-activated GIRK channels. Methadone is not a specific GIRK channel blocker. It also inhibits small conductance Ca2+-activated K+ (SK2) channels. We conclude that methadone is a full agonist at MOPrs that, as we and others have shown, induces MOPr desensitization and internalization.

Molecular Pharmacology

Frontiers in Synaptic …, 2010

The Journal of Neuroscience

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13877/full. Enzymes are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic recepto...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13883/full. Transporters are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic re...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13876/full. Catalytic receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, enzym...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13879/full. Ligand-gated ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzym...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13881/full. Other ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, nuclear hormone receptors, catalytic receptors, enzym...

British journal of pharmacology, 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nea... more The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13878/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzym...

Brain Research, May 30, 2007

Expert opinion on therapeutic targets, Jan 26, 2016

Neuroreport, 2008