Regulation of Ca2+ influx by a protein kinase C activator in chromaffin cells: differential role of P/Q- and L-type Ca2+ channels

Sena, Cristina M.; Santos, Rosa M.; Boarder, Michael R.; Rosário, Luı́s M.

doi:10.1016/s0014-2999(98)00908-x

Cited by 14 publications

(11 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The regulation of the function of L-type VDCC by serine/threonine phosphorylation has been described extensively [3,5,8,15,18,21,41,42]. Finally, although the function of L-type VDCC is reportedly regulated by tyrosine phosphorylation [16,34], under our conditions pervanadate exerted no significant effects.…”

Section: Resultsmentioning

confidence: 47%

“…Most of the protein phosphatases described can be classified as either protein serine/threonine phosphatases or protein tyrosine phosphatases [25,43,45]. In particular, the function of L-type VDCC is regulated by either serine/threonine [3,5,8,15,18,21,41,42] or tyrosine [16,34] phosphorylation. Furthermore, many proteins involved in neurotransmitter release are known to be regulated by phosphorylation [43,45].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Coupling of L-type calcium channels to neurotransmitter release at mouse motor nerve terminals

Urbano

Depetris

Uchitel

2001

Pfl�gers Archiv European Journal of Physiology

View full text Add to dashboard Cite

Previously, we have presented evidence for the presence of L-type voltage-dependent Ca2+ channels (VDCC) in 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, (acetoxymethyl)ester (BAPTA-AM)-incubated motor nerve terminals (MNTs) of the levator auris muscle of mature mice. The aim of the present work was to study the coupling of these L-type VDCC to neurotransmitter release by inhibiting protein phosphatases. We thus studied the effects of the protein phosphatase inhibitors okadaic acid (OA) and pervanadate on quantal content (QC) of transmitter release with the P/Q-type channels fully blocked. The QC was not significantly different under the three experimental conditions tested: incubation with dimethylsulphoxide (DMSO), ethylene-glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid, (acetoxymethyl)ester (EGTA-AM) and BAPTA-AM. After preincubation with OA (1 microM), but not with pervanadate, QC increased substantially in the BAPTA-AM-incubated (up to 400%) MNT, but not in those incubated with DMSO or EGTA-AM. The OA-induced increment of QC was attenuated greatly (approximately 95% reduction) by preincubation with either nitrendipine (10 microM) or calciseptine (300 nM). The effect of OA (1 microM) and pervanadate (0.1 mM) on spontaneous neurotransmitter release was also studied. After preincubation with OA, but not per-vanadate, miniature end-plate potential (MEPP) frequency increased only in the BAPTA-AM-incubated MNT (up to 700% increment). This response was attenuated (by approximately 80%) by nitrendipine (10 microM) or calciseptine (300 nM). In contrast, neither omega-agatoxin IVA (120 nM) nor omega-conotoxin GVIA (1 microM) affected this OA-induced increment significantly. We also evaluated the relationship between QC and extracellular [Ca2+] ([Ca2+]o) in BAPTA-AM-incubated MNT. Under conditions in which only P/Q-type VDCC were available to participate in neurotransmitter release, QC increased as [Ca2+]o was raised from 0.5 to 2 mM. However, when only L-type VDCC were available, QC increased when [Ca2+]o increased from 0.5 to 1 mM, but decreased significantly at 2 mM. The mean latency for P/Q-type VDCC-mediated EPP was 1.7-1.9 ms; for L-type VDCC-mediated EPP, 1.9-2.5 ms. The rise time of the L-type VDCC mediated EPP was significantly slower than that mediated by P/Q-type VDCC. Preincubation with H-7 (100 microM), a potent inhibitor of protein kinase C (PKC) and adenosine 3',5'cyclic monophosphate (cAMP)-dependent protein kinase (PKA), attenuated the OA-induced increment of both QC and MEPP frequency (50% and 70% decrement, respectively), suggesting the participation of at least these two protein kinases in the coupling of L-type VDCC. In summary, our results show coupling of L-type VDCC to neurotransmitter release when protein phosphatases are inhibited and intracellular [Ca2+] is buffered by the fast chelator BAPTA.

show abstract

Section: Resultsmentioning

confidence: 47%

Section: Introductionmentioning

confidence: 99%

Coupling of L-type calcium channels to neurotransmitter release at mouse motor nerve terminals

Urbano

Depetris

Uchitel

2001

Pfl�gers Archiv European Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…The cooperation between the influx of extracellular calcium and PKC activation has been described (Swartz, 1993, Sena et al, 1999). Our results demonstrate that α1-ARs activation could increase glutamate release by an interaction with extracellular calcium influx.…”

Section: Discussionmentioning

confidence: 99%

Activation of alpha1-adrenoceptors enhances glutamate release onto ventral tegmental area dopamine cells

2012

View full text Add to dashboard Cite

The ventral tegmental area (VTA) plays an important role in reward and motivational processes that facilitate the development of drug addiction. Glutamatergic inputs into the VTA contribute to dopamine (DA) neuronal activation related to reward and response-initiating effects in drug abuse. Previous investigations indicate that alpha1-adrenoreceptors (α1-AR) are primarily localized at presynaptic elements in the ventral midbrain. Studies from several brain regions have shown that presynaptic α1-AR activation enhance glutamate release. Therefore, we hypothesized that glutamate released onto VTA-DA neurons is modulated by pre-synaptic α1-AR. Recordings were obtained from putative VTA-DA cells of male Sprague-Dawley rats (28–50 days postnatal) using voltage clamp techniques. Phenylephrine (10 µM) and methoxamine (80 µM), both α1-AR agonists, increased AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) amplitude evoked by electrical stimulation of afferent fibers (p<0.05). This effect was blocked by the α1-AR antagonist prazosin (1 µM). Phenylephrine decreased the paired-pulse ratio and increased spontaneous EPSCs frequencies but not their amplitudes suggesting a presynaptic locus of action. No changes in miniature EPSCs (0.5 µM TTX) were observed after phenylephrine’s application which suggest that α1-AR effect was action potential dependent. Normal extra- and intracellular Ca2+ concentration seems necessary for the α1-AR effect since phenylephrine in low Ca2+ ACSF and depletion of intracellular Ca2+ stores with thapsigargin (10 µM) failed to increase the AMPA EPSCs amplitude . Chelerythrine (1 µM, PKC inhibitor) but not Rp-cAMPS (11 µM, PKA inhibitor) blocked the α1-AR activation effect on AMPA EPSCs, indicating that a PKC intracellular pathway is required. These results demonstrated that presynaptic α1-ARs activation modulates glutamatergic inputs that affect VTA-DA neurons excitability. α1-ARs action might be heterosynaptically localized at glutamatergic fibers terminating onto VTA-DA neurons. It is suggested that drug-induced changes in α1-AR could be part to the neuroadaptations occurring in the mesocorticolimbic circuitry during the addiction process.

show abstract

“…PKC also regulates other types of Ca 2ϩ channels in a variety of cells. L-type voltage-dependent Ca 2ϩ channels are inhibited by activation of PKC in adrenal chromaffin cells [Sena et al, 1999] and PKC-␦ mediates ethanol-induced up-regulation of L-type Ca 2ϩ channels in PC12 cells [Gerstin et al, 1998]. Maintenance of Ca 2ϩ current through N-type voltage-dependent Ca 2ϩ channels in rat dorsal root ganglion neurons also requires endogenous PKC [King et al, 1999].…”

Section: Discussionmentioning

confidence: 99%

Regulation of (1-3)-?-glucan-stimulated Ca2+ influx by protein kinase C in NR8383 alveolar macrophages

Ac¹,

X²,

Liu³

et al. 2000

J. Cell. Biochem.

View full text Add to dashboard Cite

Stimulation of (1-3)-beta-glucan receptors results in Ca(2+) influx through receptor-operated channels in alveolar macrophages (AMs), but the mechanism(s) regulating Ca(2+) influx is still undefined. In this study we investigated the role of protein kinase C (PKC) regulation of Ca(2+) influx in the NR8383 AM cell line using the particulate (1-3)-beta-glucan receptor agonist zymosan. PKC inhibition with calphostin C (CC) or bisindolymaleimide I (BSM) significantly reduced zymosan-induced Ca(2+) influx, whereas activation of PKC with phorbol-12-myristate 13-acetate (PMA) or 1, 2-dioctanoyl-sn-glycerol (DOG) mimicked zymosan, inducing a concentration-dependent Ca(2+) influx. This influx was dependent on extracellular Ca(2+) and inhibited by the receptor-operated Ca(2+) channel blocker SK&F96365, indicating that zymosan and PKC activate Ca(2+) influx through a similar pathway. NR8383 AMs expressed one new PKC isoform (delta) and two atypical PKC isoforms (iota and lambda), but conventional PKC isoforms were not present. Stimulation with zymosan resulted in a translocation of PKC-delta from the cytosol to the membrane fraction. Furthermore, inhibition of protein tyrosine kinases (PTKs) with genistein prevented zymosan-stimulated Ca(2+) influx and PKC-delta translocation. These results suggest that PKC-delta plays a critical role in regulating (1-3)-beta-glucan receptor activated Ca(2+) influx in NR8383 AMs and PKC-delta translocation is possibly dependent on PTK activity.

show abstract

Regulation of Ca2+ influx by a protein kinase C activator in chromaffin cells: differential role of P/Q- and L-type Ca2+ channels

Cited by 14 publications

References 57 publications

Coupling of L-type calcium channels to neurotransmitter release at mouse motor nerve terminals

Coupling of L-type calcium channels to neurotransmitter release at mouse motor nerve terminals

Activation of alpha1-adrenoceptors enhances glutamate release onto ventral tegmental area dopamine cells

Regulation of (1-3)-?-glucan-stimulated Ca2+ influx by protein kinase C in NR8383 alveolar macrophages

Contact Info

Product

Resources

About