Molecular Mechanism of Convergent Regulation of Brain Na+ Channels by Protein Kinase C and Protein Kinase A Anchored to AKAP-15

Cantrell, Angela R.; Tibbs, Victoria C.; Yu, Frank H.; Murphy, Brian J.; Sharp, Elizabeth M.; Qu, Yusheng; Catterall, William A.; Scheuer, Todd

doi:10.1006/mcne.2002.1162

Cited by 82 publications

(84 citation statements)

References 31 publications

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“…؉ currents in mouse hippocampal neurons by OAG OAG is a membrane-permeant PKC activator that reduces peak Na ϩ current in cultured brain neurons, acutely isolated rat hippocampal neurons, and Chinese hamster ovary or tsA-201 cells in which Na v 1.2␣ Na ϩ channels have been expressed Cantrell et al, 1996Cantrell et al, , 2002. We confirmed these results for acutely isolated mouse hippocampal neurons using 50 M OAG, which produces a maximal effect in rat hippocampal neurons (Cantrell et al, 1996).…”

Section: Reduction Of Peak Nasupporting

confidence: 75%

“…؉ channels in hippocampal neurons The diacylglycerol analog OAG effectively activates endogenous PKC isozymes that are responsible for modulation of Na ϩ channels by muscarinic acetylcholine receptors (Cantrell et al, 1996(Cantrell et al, , 2002. Because conventional (␣, ␤, and ␥) and novel (␦, ⑀, , and ) isozymes respond to OAG, whereas atypical isozymes ( and /) do not, these results suggest that atypical PKCs are not involved in modulation of Na ϩ channels.…”

Section: Pkc⑀ Specifically Modulates Namentioning

confidence: 99%

“…In addition, four different Na ϩ channels are expressed in the CNS (Goldin, 2001). Na V 1.1 channels have virtually identical PKC phosphorylation sites to Na V 1.2 (Cantrell et al, 2002), suggesting similar regulation, whereas Na V 1.3 and Na V 1.6 channels have amino acid changes flanking the potentially phosphorylated serines that may alter their regulation. Future research will likely identify isozymespecific consequences of PKC regulation of specific subtypes of Na ϩ channels.…”

Section: Pkc⑀ Links Namentioning

confidence: 99%

“…The sites of PKC phosphorylation are on the ␣ subunit (Costa and Catterall, 1984;Murphy and Catterall, 1992). Serines 554, 573, and 576 in the intracellular linker between domains I and II and serine 1506 in the inactivation gate between domains III and IV are required for modulation (West et al, 1991;Cantrell et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Specific Modulation of Na⁺Channels in Hippocampal Neurons by Protein Kinase Cϵ

Chen¹,

Cantrell²,

Messing³

et al. 2005

J. Neurosci.

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Acetylcholine binding to muscarinic acetylcholine receptors activates G-proteins, phospholipase C, and protein kinase C (PKC), which phosphorylates brain Na ϩ channels and reduces peak Na ϩ current in hippocampal neurons. Because multiple PKC isozymes with different regulatory properties are expressed in hippocampal neurons, we investigated which ones are responsible for mediating this effect. The diacylglycerol analog oleoylacetylglycerol (OAG) reduced the amplitude of Na ϩ current in dissociated mouse hippocampal neurons by 28.5 Ϯ 5.3% ( p Ͻ 0.01). The reduction of peak Na ϩ current was similar with Ca 2ϩ -free internal solution and in 92 nM internal Ca 2ϩ , suggesting that calcium-dependent, conventional PKC isozymes were unlikely to mediate this response. Gö6976, which inhibits conventional PKC isozymes, reduced the effect of PKC activators only slightly, whereas rottlerin, which inhibits PKC␦ preferentially at 5 M, had no effect. Ro-31-8425 (20 nM), which inhibits conventional PKC isozymes, did not reduce the response to OAG. However, higher concentrations of Ro-31-8425 (100 nM or 1 M) that inhibit novel PKC isozymes effectively blocked OAG inhibition of Na ϩ current. Inclusion of a selective PKC⑀-anchoring inhibitor peptide (PKC⑀-I) in the recording pipette prevented the reduction of peak Na ϩ current by OAG, whereas an anchoring inhibitor peptide specific for PKC␤ and an inactive scrambled PKC⑀-I peptide had no effect. In addition, OAG had no effect on Na ϩ current in hippocampal neurons from PKC⑀ null mice. Overall, our data from four experimental approaches indicate that anchored PKC⑀ is the isozyme responsible for PKC-mediated reduction of peak Na ϩ currents in mouse hippocampal neurons.

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Section: Reduction Of Peak Nasupporting

confidence: 75%

Section: Pkc⑀ Specifically Modulates Namentioning

confidence: 99%

Section: Pkc⑀ Links Namentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Specific Modulation of Na⁺Channels in Hippocampal Neurons by Protein Kinase Cϵ

Chen¹,

Cantrell²,

Messing³

et al. 2005

J. Neurosci.

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“…Activating the 5-HT2C subtype of serotonin receptors in prefrontal cortex neurons results in a negative shift in the voltage-dependence of fast inactivation accompanied with a reduction of the peak current due to a PKCmediated phosphorylation process (Carr et al, 2002). Concurrent phosphorylation by PKA seems necessary for the maximal current reduction (Cantrell et al, 2002). These mechanisms can be activated by various neurotransmitters including serotonin (Cantrell and Catterall, 2001).…”

Section: Antidepressantsmentioning

confidence: 99%

Protein Kinases and Pain

Funez¹,

Souza²,

Pandossio³

et al. 2012

Protein Kinases

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Enhancement of AMPA currents and GluR1 membrane expression through PKA‐coupled adenosine A_2A receptors

2010

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Phosphorylation of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by Protein Kinase A (PKA) is known to regulate AMPA receptor (AMPAR) trafficking and stabilization at the postsynaptic membrane, which in turn is one of the key mechanisms by which synaptic transmission and plasticity are tuned. However, not much is known as to how Gs-coupled receptors contribute to endogenous PKA-mediated regulation of AMPA receptor function. Here we report that activation of the excitatory A(2A) adenosine receptor by 2-[4-(2-p-carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680, 1-30 nM) facilitates AMPA-evoked currents in CA1 pyramidal neurons, by a mechanism dependent on PKA activation, but not on protein synthesis. This modulation of AMPA currents was mimicked by forskolin (1 μM) and did not occur in stratum radiatum interneurons. Superfusion of the A(2A) receptor agonist also caused an increase in the amplitude of miniature excitatory postsynaptic currents (mEPSCs), as well as in the membrane levels of GluR1 subunits phosphorylated at the PKA site (Ser845). The impact of this increase on GluR1-containing AMPA receptor expression was evidenced by the potentiation of LTP at the CA3-CA1 synapse that followed brief activation of A(2A) receptors. We thus propose that in conditions of increased adenosine availability, A(2A) receptor activation is responsible for setting part of the endogenous GluR1 Ser-845 phosphorylation tonus and hence, the availability of the GluR1-containing AMPA receptor extrasynaptic pool for synaptic insertion and reinforcement of synaptic strength.

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Molecular Mechanism of Convergent Regulation of Brain Na+ Channels by Protein Kinase C and Protein Kinase A Anchored to AKAP-15

Cited by 82 publications

References 31 publications

Specific Modulation of Na⁺Channels in Hippocampal Neurons by Protein Kinase Cϵ

Specific Modulation of Na⁺Channels in Hippocampal Neurons by Protein Kinase Cϵ

Protein Kinases and Pain

Enhancement of AMPA currents and GluR1 membrane expression through PKA‐coupled adenosine A_2A receptors

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Molecular Mechanism of Convergent Regulation of Brain Na+ Channels by Protein Kinase C and Protein Kinase A Anchored to AKAP-15

Cited by 82 publications

References 31 publications

Specific Modulation of Na+Channels in Hippocampal Neurons by Protein Kinase Cϵ

Specific Modulation of Na+Channels in Hippocampal Neurons by Protein Kinase Cϵ

Protein Kinases and Pain

Enhancement of AMPA currents and GluR1 membrane expression through PKA‐coupled adenosine A2A receptors

Contact Info

Product

Resources

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Specific Modulation of Na⁺Channels in Hippocampal Neurons by Protein Kinase Cϵ

Specific Modulation of Na⁺Channels in Hippocampal Neurons by Protein Kinase Cϵ

Enhancement of AMPA currents and GluR1 membrane expression through PKA‐coupled adenosine A_2A receptors