Enhancement of calcium current in Aplysia neurones by phorbol ester and protein kinase C

DeRiemer, Susan A.; Strong, Judith A.; Albert, Katherine A.; Greengard, Paul; Kaczmarek, Leonard K.

doi:10.1038/313313a0

Cited by 460 publications

(156 citation statements)

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“…Slowly inactivating Ca current is reduced by PKC activation in rat DRG cells , cultured mouse neurons (Werz and Macdonald, 1987), and snail neurons (Hammond et al, 1987). A similar current is enhanced in ApZysiu (DeRiemer et al, 1985) and Hermissenda (Alkon et al, 1986;Farley and Auerbach, 1986). In Aplysia, K currents are not affected, while in Hermissenda, Z, is a target for PKC regulation and ZK is not affected.…”

Section: Discussionmentioning

confidence: 69%

Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons

1988

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Whole-cell voltage-clamp techniques were used to study the effects of the protein kinase C (PKC) activators phorbol esters and OAG on Ca and K currents in differentiated neurons acutely dissociated from adult hippocampus and in tissue-cultured neurons from fetal hippocampus. PKC activators had selective depressant effects on K currents, with persistent currents (IK and IK-Ca) being reduced and transient current (IA) being unaffected. In both cell types we recorded both high-voltage- activated, noninactivating (L-type) and high-voltage-activated, rapidly inactivating (N-type) Ca current. A low-voltage-activated, rapidly inactivating (T-type) Ca current was also recorded in tissue-cultured neurons but not in acutely dissociated neurons. PKC activators markedly reduced N-type current with less effect on L-type and no effect on T- type Ca current. Effects of PKC activators could be reversed with washing or with application of PKC inhibitors H-7 or polymyxin-B, an effect that could not be attributed to inhibition of cAMP-dependent protein kinase. The Ca/calmodulin inhibitor calmidazolium was ineffective in reversing the actions of PKC activators. Using whole- cell voltage-clamp techniques, we have demonstrated that hippocampal neurons possess 3 distinguishable components of calcium current. Distinct K currents were also observed. Our data strongly support the hypothesis that both Ca and K currents are selectively regulated by PKC and that these effects occur directly on the postsynaptic neuron.

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Section: Discussionmentioning

confidence: 69%

Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons

1988

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“…Enhanced calcium current results from insertion of Ca V 2 channels into the plasma membrane Previous data has shown that the PKC activator TPA increases calcium currents and enhances the calcium component of action potentials in BCNs (DeRiemer et al, 1985). These actions of TPA are mimicked by the structurally unrelated diacylglycerol activators of PKC and by direct microinjection of this enzyme, and can be prevented by PKC inhibitors including pseudosubstrate peptide inhibitors (Conn and Kaczmarek, 1989;Conn et al, 1989a,b).…”

Section: Resultsmentioning

confidence: 99%

“…One component of the response of BCNs to stimulation is the activation of protein kinase C (PKC) (DeRiemer et al, 1985;Strong et al, 1987;White et al, 1998). This enzyme rapidly increases calcium current and expands growth cones, which, after coactivation of other kinases, become secretory endings packed with neuropeptide granules (Forscher et al, 1987;Knox et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

“…BCNs contain two physiologically characterized calcium channels (Ca V 1, Ca V 2), one of which (Ca V 2) is normally localized to intracellular vesicles and is sensitive to PKC (White et al, 1998). Activation of PKC with phorbol esters or diacylglycerols rapidly and reproducibly enhances voltage dependent calcium current by twofold to threefold (DeRiemer et al, 1985;Strong et al, 1987;Jonas et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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PKC-Induced Intracellular Trafficking of Ca_V2 Precedes Its Rapid Recruitment to the Plasma Membrane

Zhang

Helm²,

Senatore³

et al. 2008

J. Neurosci.

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Activation of protein kinase C (PKC) potentiates secretion in Aplysia peptidergic neurons, in part by inducing new sites for peptide release at growth cone terminals. The mechanisms by which ion channels are trafficked to such sites are, however, not well understood. We now show that PKC activation rapidly recruits new Ca V 2 subunits to the plasma membrane, and that recruitment is blocked by latrunculin B, an inhibitor of actin polymerization. In contrast, inhibition of microtubule polymerization selectively prevents the appearance of Ca V 2 subunits only at the distal edge of the growth cone. In resting neurons, Ca V 2-containing organelles reside in the central region of growth cones, but are absent from distal lamellipodia. After activation of PKC, these organelles are transported on microtubules to the lamellipodium. The ability to traffic to the most distal sites of channel insertion inside the lamellipodium does, therefore, not require intact actin but requires intact microtubules. Only after activation of PKC do Ca V 2 channels associate with actin and undergo insertion into the plasma membrane.

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“…Alternatively phorbol esters may regulate the activity of Ca2"-channels (De Riemer et al, 1985;Wakade et al, 1986). However, observations about phorbol ester effects on Ca2"-channels have, as yet, been contradictory: in Aplysia neurones phorbol esters directly augmented Ca2+-currents (De Riemer et al, 1985), whereas the enhancement of dopamine release from brain neurones was independent of extracellular Ca2"-concentrations and appeared to be due to increases in the affinity of Ca2+ to PKC (Zurgil & Zisapel, 1985). Recently, even an inhibitory control of voltage-gated Ca2"-channels exerted by phorbol esters has been shown (Di Virgilio et al, 1986;Messing et al, 1986 …”

Section: Discussionmentioning

confidence: 99%

Protein kinase C activation and α₂‐autoreceptor‐modulated release of noradrenaline

Allgaier

Hertting

Huang

et al. 1987

British J Pharmacology

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1Effects of phorbol esters on the evoked noradrenaline release were studied in slices of the rabbit hippocampus, labelled with [3HJ-noradrenaline, superfused continuously with a medium containing the reuptake inhibitor cocaine and stimulated electrically for 2 min (stimulation parameters: 2 ms, 24mA, 5Vcm-', 3 or 0.3Hz).2 The electrically-evoked overflow of [3H]-noradrenaline in the slices was increased in a concentration-dependent manner by the protein kinase C (PKC) activators 12-0-tetradecanoylphorbol 13-acetate (TPA) and 4f-phorbol 12,13-dibutyrate (4p-PDB). Phorbol esters, which do not activate PKC, 4-0-methyl-TPA and 4a-PDB, showed no effect on neurotransmitter release. The effect of4P-PDB was abolished in the presence of tetrodotoxin and in the absence of calcium. The PKC inhibitor polymyxin B inhibited the evoked noradrenaline release.3 In the presence of 4P-PDB the inhibitory effects of the o2-adrenoceptor agonist clonidine or the facilitatory effects ofthe z2-adrenoceptor antagonist yohimbine seemed to be modified only by changes in the concentration of noradrenaline in the synaptic region. At a stimulation frequency of 3 Hz the inhibitory action of clonidine was reduced whereas the facilitatory effect of the yohimbine was even slightly enhanced by the phorbol ester. At 0.3 Hz and in the presence of 4P-PDB the effect of clonidine remained and that of yohimbine was strongly enhanced. 4 Pretreatment of the slices with islet-activating protein or N-ethylmaleimide significantly reduced the enhancement of noradrenaline release caused by 4P-PDB. It is possible that a regulatory N-protein is involved in steps following PKC activation. 5 These results suggest that PKC participates in the mechanism of action-potential-induced noradrenaline release from noradrenergic nerve terminals of the rabbit hippocampus and that effects on the autoinhibitory feedback system were not responsible for the 4P-PDB-induced increase of neurotransmitter release.

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Enhancement of calcium current in Aplysia neurones by phorbol ester and protein kinase C

Cited by 460 publications

References 14 publications

Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons

Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons

PKC-Induced Intracellular Trafficking of Ca_V2 Precedes Its Rapid Recruitment to the Plasma Membrane

Protein kinase C activation and α₂‐autoreceptor‐modulated release of noradrenaline

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Enhancement of calcium current in Aplysia neurones by phorbol ester and protein kinase C

Cited by 460 publications

References 14 publications

Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons

Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons

PKC-Induced Intracellular Trafficking of CaV2 Precedes Its Rapid Recruitment to the Plasma Membrane

Protein kinase C activation and α2‐autoreceptor‐modulated release of noradrenaline

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PKC-Induced Intracellular Trafficking of Ca_V2 Precedes Its Rapid Recruitment to the Plasma Membrane

Protein kinase C activation and α₂‐autoreceptor‐modulated release of noradrenaline