Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K+channels of Aplysia sensory neurones in cell-free membrane patches

Shuster, Malcolm D.; Camardo, Joseph S.; Siegelbaum, S. A.; Kandel, Eric R.

doi:10.1038/313392a0

Cited by 267 publications

(125 citation statements)

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“…In the presence of S-Ht31, the EPSP amplitude increased by only 25.1 Ϯ 8.1% (n ϭ 10) after treatment with 5-HT compared with an expected increase of 95.5 Ϯ 10.6% (n ϭ 10) in the presence of S-Ht31P, an inactive control peptide. Because short-term facilitation is a local response restricted to sensory neuron-L7 terminals where the activity of PKA is essential (Shuster et al, 1985;Braha et al, 1990;Clark and Kandel, 1993;Emptage and Carew, 1993;Wu et al, 1995;Sun and Schacher, 1996;Sherff and Carew, 1999;Angers et al, 2002), this result suggests that disruption of the binding between RII and AKAPs at sensory neuron terminals prevents PKA from phosphorylating synaptic proteins that are critical for the plasticity.…”

Section: Resultsmentioning

confidence: 90%

“…Two likely synaptic substrates for PKA in Aplysia are the S-type K ϩ channel (Shuster et al, 1985) and synapsin (Angers et al, 2002). Phosphorylation of the channel by PKA produces hyperexcitability and broadening of the action potential (Shuster et al, 1985;Belardetti et al, 1987).…”

Section: Rii-akap Binding and The Compartmentalization Of The Camp-pkmentioning

confidence: 99%

“…PKA is essential for both forms (Castellucci et al, 1980;Kandel and Schwartz, 1982;Schacher et al, 1988;Conn et al, 1989). In short-term facilitation produced by brief application of a facilitatory neurotransmitter serotonin (5-HT), activation of PKA leads to the phosphorylation of existing synaptic proteins, resulting in enhanced transmitter release (Shimahara and Tauc, 1978;Castellucci et al, 1982;Shuster et al, 1985). During longterm facilitation produced by repeated applications of 5-HT, PKA remains activated for at least 24 hr (Greenberg et al, 1987;Sweatt and Kandel, 1989;Muller and Carew, 1998).…”

Section: Introductionmentioning

confidence: 99%

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The Two Regulatory Subunits ofAplysiacAMP-Dependent Protein Kinase Mediate Distinct Functions in Producing Synaptic Plasticity

Liu¹,

Hu²,

Schacher³

et al. 2004

J. Neurosci.

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Activation of the cAMP-dependent protein kinase (PKA) is critical for both short-and long-term facilitation in Aplysia sensory neurons. There are two types of the kinase, I and II, differing in their regulatory (R) subunits. We cloned Aplysia RII; RI was cloned previously. Type I PKA is mostly soluble in the cell body whereas type II is enriched at nerve endings where it is bound to two prominent A kinaseanchoring-proteins (AKAPs). Disruption of the binding of RII to AKAPs by Ht31, an inhibitory peptide derived from a human thyroid AKAP, prevents both the short-and the long-term facilitation produced by serotonin (5-HT). During long-term facilitation, RII is transcriptionally upregulated; in contrast, the amount of RI subunits decreases, and previous studies have indicated that the decrease is through ubiquitin-proteosome-mediated proteolysis. Experiments with antisense oligonucleotides injected into the sensory neuron cell body show that the increase in RII protein is essential for the production of long-term facilitation. Using synaptosomes, we found that 5-HT treatment causes RII protein to increase at nerve endings. In addition, using reverse transcription-PCR, we found that RII mRNA is transported from the cell body to nerve terminals. Our results suggest that type I operates in the nucleus to maintain cAMP response element-binding protein-dependent gene expression, and type II PKA acts at sensory neuron synapses phosphorylating proteins to enhance release of neurotransmitter. Thus, the two types of the kinase have distinct but complementary functions in the production of facilitation at synapses of an identified neuron.

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Section: Resultsmentioning

confidence: 90%

Section: Rii-akap Binding and The Compartmentalization Of The Camp-pkmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Two Regulatory Subunits ofAplysiacAMP-Dependent Protein Kinase Mediate Distinct Functions in Producing Synaptic Plasticity

Liu¹,

Hu²,

Schacher³

et al. 2004

J. Neurosci.

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“…For example, TREK-1 (9) and its putative invertebrate homologue, the Aplysia S-K ϩ channel (17), are inhibited by a cyclic AMP-dependent protein kinase phosphorylation in the C-terminal cytoplasmic tail (18,19). In both channels, the effect is due to a change in the open probability of the channel.…”

Section: Discussionmentioning

confidence: 99%

Activation of Protein Kinase C ϵ Inhibits the Two-pore Domain K+ Channel, TASK-1, Inducing Repolarization Abnormalities in Cardiac Ventricular Myocytes

Besana

Barbuti

Tateyama

et al. 2004

Journal of Biological Chemistry

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Activation of the platelet-activating factor (PAF) receptor leads to a decrease in outward current in murine ventricular myocytes by inhibiting the TASK-1 channel. TASK-1 carries a background or "leak" current and is a member of the two-pore domain potassium channel family. Its inhibition is sufficient to delay repolarization, causing prolongation of the action potential duration, and in some cases, early after depolarizations. We set out to determine the cellular mechanisms that control regulation of TASK-1 by PAF. Inhibition of TASK-1 via activation of the PAF receptor is protein kinase C (PKC)-dependent. Using isoform-specific PKC inhibitor or activator peptides in patch clamp experiments, we now demonstrate that activation of PKC⑀ is both necessary and sufficient to regulate murine TASK-1 current in a heterologous expression system and to induce repolarization abnormalities in isolated myocytes. Furthermore, site-directed mutagenesis studies have identified threonine 381, in the C-terminal tail of murine TASK-1, as a critical residue in this regulation.Regulation of cardiac function depends on the appropriate cumulative activity of numerous ion channels in individual cardiomyocytes that are responsible for the sequential depolarization-repolarization cycle known as the action potential (AP). 1 Although the major currents contributing to the AP have been described (1), additional small currents at specific points of low conductance in the AP cycle are sufficient to induce repolarization abnormalities in isolated cells (2, 3) and therefore arrhythmias in situ. These arrhythmias may contribute to the electrical abnormalities that lead to sudden death after myocardial infarction, which persists as the number one cause of death in the United States. We have focused on one channel that has been proposed to contribute to cardiac arrhythmias, TASK-1, a member of the recently described family of two-pore domain potassium channels (4).The two-pore domain K channel family is composed of at least 15 different members. These channels are widely distributed in excitable tissue, primarily in the brain and heart, and in general are responsive to environmental cues such as temperature, pH, and stretch (5, 6). Several are also regulated by lipids such as arachidonic acid or platelet-activating factor (PAF) (7-9). PAF is an inflammatory phospholipid that has been linked to arrhythmogensis in isolated canine ventricular myocytes (10). We have recently shown that PAF regulates the TASK-1 channel and determined that the arrhythmogenic effect of the stable PAF analog, carbamyl-platelet-activating factor (C-PAF) in mouse cardiomyocytes, is due to the inhibition of TASK-1 current in a protein kinase C (PKC)-dependent manner (2).In this study, we elucidate the molecular mechanism of the C-PAF effect on TASK-1 current by identifying the ⑀ isoform of PKC (PKC⑀) as a critical component in PAFR signaling. In addition, using site-directed mutagenesis, we have tentatively identified the critical residue that is the target for PKC in the mu...

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“…The first involves closure of K+ channels, which broadens the presynaptic action potential, increasing Ca2+ influx at transmitter release sites (Klein et al, 1982;Siegelbaum et al, 1982;Baxter and Byrne, 1990;Hochner and Kandel, 1992;Eliot et al, 1993). This effect is mediated in part by CAMP-dependent protein kinase (Castellucci et al, 1982;Shuster et al, 1985;Goldsmith and Abrams, 1992). The second process is independent of changes in the action potential and involves either vesicle mobilization or a direct enhancement of exocytosis (Hochner et al, 1986b).…”

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confidence: 99%

Pairing-specific, activity-dependent presynaptic facilitation at Aplysia sensory-motor neuron synapses in isolated cell culture

et al. 1994

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Synapses made by Aplysia sensory neurons onto motor- and interneuron followers in the intact nervous system exhibit an associative form of synaptic facilitation that is thought to contribute to classical conditioning of the animal's gill and siphon withdrawal reflex (Hawkins et al., 1983; Walters and Byrne, 1983). Here we demonstrate that a similar associative facilitation can be induced between individual sensory and motor neurons isolated in culture. Pairing tetanic stimulation with either of two facilitatory transmitters, 5-HT or small cardioactive peptide, considerably prolongs facilitation compared to either tetanus or transmitter alone. When corrected for the depression that occurs simply in response to low-frequency testing, the facilitation produced by one pairing trial does not decay for more than 20 min after training. This facilitation requires the temporal pairing (0.5 sec forward interstimulus interval) of the two stimuli, tetanus and 5-HT. Delivering the same two stimuli in an unpaired fashion (1 min forward interval) fails to produce the long-lasting effect. Measurements of spontaneous transmitter release during either paired or unpaired training reveal no changes in unitary mEPSP or mEPSC (“mini”) amplitude, indicating that the facilitation involves a presynaptic mechanism. While both forms of training dramatically increase the initial frequency of spontaneous release, mini frequency does not remain elevated as long as the evoked EPSP following paired training, nor does paired training specifically enhance spontaneous release frequency. Pairing-specific facilitation was not blocked by the protein kinase C inhibitor H7. In contrast, the same training procedure produced pairing-specific increases of sensory neuron excitability and action potential width, suggesting that cAMP-mediated processes are involved in the paired effect. Although Ca2+ influx is necessary for the associative effect (Abrams, 1985), we find that the facilitation does not require influx through L-type voltage-gated Ca2+ channels, since the effect was not blocked by the dihydropyridine antagonist nitrendipine. Together, these findings indicate that the mechanism underlying associative, activity-dependent facilitation is intrinsic to the sensory neuron synapse, that it is presynaptically mediated by processes unique to evoked synaptic transmission, and that it appears to involve a pairing-specific broadening of the presynaptic action potential, allowing enhanced Ca2+ influx through the dihydropyridine- insensitive channels responsible for release.

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Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K+channels of Aplysia sensory neurones in cell-free membrane patches

Cited by 267 publications

References 24 publications

The Two Regulatory Subunits ofAplysiacAMP-Dependent Protein Kinase Mediate Distinct Functions in Producing Synaptic Plasticity

The Two Regulatory Subunits ofAplysiacAMP-Dependent Protein Kinase Mediate Distinct Functions in Producing Synaptic Plasticity

Activation of Protein Kinase C ϵ Inhibits the Two-pore Domain K+ Channel, TASK-1, Inducing Repolarization Abnormalities in Cardiac Ventricular Myocytes

Pairing-specific, activity-dependent presynaptic facilitation at Aplysia sensory-motor neuron synapses in isolated cell culture

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