A Post-Burst Afterdepolarization Is Mediated by Group I Metabotropic Glutamate Receptor-Dependent Upregulation of Cav2.3 R-Type Calcium Channels in CA1 Pyramidal Neurons

Park, Jin-Yong; Remy, Stefan; Varela, Juan Carlos; Cooper, Donald; Chung, Sungkwon; Kang, Ho-Won; Lee, Jung-Ha; Spruston, Nelson

doi:10.1371/journal.pbio.1000534

Cited by 41 publications

(56 citation statements)

References 57 publications

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“…All of these manipulations inhibited the induction of the ADP, as indicated by the reduced magnitudes of the Δ post-burst potential (Figure 3C). We showed previously that activation of group I mGluRs by a selective agonist (DHPG) produced a post-burst ADP with similar pharmacology (Park et al, 2010). Here, we performed further experiments indicating that this effect was not produced by other receptors which are also coupled to G q/11 signaling (α 1 adrenergic receptor and 5-HT 2 serotonergic receptor; data not shown), suggesting that it is somewhat specific to mAChR and group I mGluR activation in these neurons.…”

Section: Resultsmentioning

confidence: 94%

“…Transverse hippocampal slices, 300 μm thick, were prepared from male Wistar rats (25- to 35-day-old) and from either wild type (C57BL/6J) or Ca v 2.3 knockout male mice (22- to 28-day-old) using standard procedures (Park et al, 2010). Animals were deeply anesthetized with halothane or isoflurane, perfused intracardially with ice-cold artificial CSF (ACSF), and decapitated.…”

Section: Methodsmentioning

confidence: 99%

“…Their stimulation triggers phospholipase C activation, mobilization of intracellular Ca 2+ , and ultimately modulation of multiple types of ion channels (Pin and Duvoisin, 1995; Anwyl, 1999). We recently demonstrated that activation of group I mGluRs eliminated the post-burst AHP and produced an afterdepolarization (ADP) through upregulation of Ca v 2.3 R-type calcium channels (Park et al, 2010). While multiple studies have reported that activation of mAChRs also induces changes in the AHP, resulting in enhanced excitability (Benardo and Prince, 1982; Cole and Nicoll, 1984a, 1984b; McCormick and Prince, 1986; Kawasaki et al, 1999; McQuiston and Madison, 1999; Lawrence et al, 2006), it is poorly understood which receptor subtypes, signaling mechanisms, and ion channels are responsible for the mAChR-mediated modulation of excitability, particularly in hippocampal CA1 pyramidal neurons.…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Actions of Metabotropic Acetylcholine and Glutamate Receptors on the Excitability of Hippocampal CA1 Pyramidal Neurons

Park

Spruston

2012

J. Neurosci.

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A variety of neurotransmitters are responsible for regulating neural activity during different behavioral states. Unique responses to combinations of neurotransmitters provide a powerful mechanism by which neural networks could be differentially activated during a broad range of behaviors. Here, we show, using whole-cell recordings in rat hippocampal slices, that group I metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors (mAChRs) synergistically increase the excitability of hippocampal CA1 pyramidal neurons by converting the post-burst afterhyperpolarization (AHP) to an afterdepolarization (ADP) via a rapidly reversible upregulation of Cav2.3 R-type calcium channels. Co-activation of mAChRs and mGluRs also induced a long-lasting enhancement of the responses mediated by each receptor type. These results suggest that cooperative signaling via mAChRs and group I mGluRs could provide a mechanism by which cognitive processes may be modulated by conjoint activation of two separate neurotransmitter systems.

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Section: Resultsmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synergistic Actions of Metabotropic Acetylcholine and Glutamate Receptors on the Excitability of Hippocampal CA1 Pyramidal Neurons

Park

Spruston

2012

J. Neurosci.

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“…Activation of mGluR5 induces phosphatidylinositol hydrolysis via phospholipase C, which releases intracellular IP3-sensitive Ca 2+ stores. It further activates ryanodine-sensitive Ca 2+ stores and alters the activity of different voltage-gated channels (Gerber et al 1992;Swartz and Bean 1992;Fagni et al 2000;Sanchez-Prieto et al 2004;Park et al 2010;Zheng and Raman 2011). Additionally, mGluR5 activation enhances glutamate-evoked currents through the NMDA receptor (Fitzjohn et al 1996).…”

Section: Other Receptors and Channels Targeted By Canmentioning

confidence: 99%

Neural functions of calcineurin in synaptic plasticity and memory: Figure 1.

2012

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Major brain functions depend on neuronal processes that favor the plasticity of neuronal circuits while at the same time maintaining their stability. The mechanisms that regulate brain plasticity are complex and engage multiple cascades of molecular components that modulate synaptic efficacy. Protein kinases (PKs) and phosphatases (PPs) are among the most important of these components that act as positive and negative regulators of neuronal signaling and plasticity, respectively. In these cascades, the PP protein phosphatase 2B or calcineurin (CaN) is of particular interest because it is the only Ca 2+ -activated PP in the brain and a major regulator of key proteins essential for synaptic transmission and neuronal excitability. This review describes the primary properties of CaN and illustrates its functions and modes of action by focusing on several representative targets, in particular glutamate receptors, striatal enriched protein phosphatase (STEP), and neuromodulin (GAP43), and their functional significance for synaptic plasticity and memory.

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“…Besides classical biochemical investigations, the large scale Y2H screening has become crucial for the identification of novel protein interactions and even proteome-wide interaction maps [10], as well as quantitative proteomic approaches have identified the nano-environment of voltage-gated Ca 2+ channels [11]. Such approaches are needed and provide important information for the functional involvement of the Ca V 2.3 Ca 2+ channel and its interaction partners in molecular processes of hippocampal excitability [12,13] and its disturbance in convulsive diseases [14].…”

Section: Introductionmentioning

confidence: 99%

Ca<sub>v</sub>2.3 Ca<sup>2+</sup> Channel Interacts with the G1-subunit of V-ATPase

Kanthavel

Kamp

Siapich

et al. 2011

Cell Physiol Biochem

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Background: Calcium channels are essential in coupling action potential to signal transduction in cells. There are several types of calcium channels, which can be pharmacologically classified as L-, N-, P/Q-, R- and T-type. But molecular basis of R-type channels is less clearly understood compared the other channel types. Therefore the current study aims at understanding the molecular functions of R-type calcium channels by identifying interaction partners of the channel. Methods: In order to do so, a yeast two hybrid (Y2H) screen, with carboxy terminus of α1 subunit of the channel, as the bait, was performed. G1 subunit of v-ATPase was identified as a putative interaction partner of human Ca_v2.3 by using the Y2H screening. The interaction was confirmed by immunoprecipitation. To study the functional importance of the interaction, bafilomycin A₁, a potent and specific inhibitor of v-ATPase was used in patch-clamp recordings in Ca_v2.3 stably-transfected HEK-293 cells (2C6) as well as in electroretinography of the isolated bovine retina expressing R-type Ca²⁺ channels. Results: G1 subunit of v-ATPase interacts with C-terminal tail of Ca_v2.3 and bafilomycin A₁ reduces Ca_v2.3 mediated calcium currents. Additionally peak I_Ca is inhibited in retinal signal transduction when recorded as ERG b-wave. Conclusions: The results suggest that v-ATPase interacts physically and also functionally with Ca_v2.3. This is the first demonstration of association of Ca_v2.3 C-terminus with a protein complex which is involved in transmembrane signalling.

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A Post-Burst Afterdepolarization Is Mediated by Group I Metabotropic Glutamate Receptor-Dependent Upregulation of Cav2.3 R-Type Calcium Channels in CA1 Pyramidal Neurons

Abstract: The excitability of hippocampal pyramidal neurons is regulated by activation of metabotropic glutamate receptors, an effect that is mediated by modulation of R-type calcium channels.

Cited by 41 publications

References 57 publications

Synergistic Actions of Metabotropic Acetylcholine and Glutamate Receptors on the Excitability of Hippocampal CA1 Pyramidal Neurons

Synergistic Actions of Metabotropic Acetylcholine and Glutamate Receptors on the Excitability of Hippocampal CA1 Pyramidal Neurons

Neural functions of calcineurin in synaptic plasticity and memory: Figure 1.

Ca<sub>v</sub>2.3 Ca<sup>2+</sup> Channel Interacts with the G1-subunit of V-ATPase

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