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

Doerner, Diane; Pitler, Thomas A.; Alger, Bradley E.

doi:10.1523/jneurosci.08-11-04069.1988

Cited by 157 publications

(102 citation statements)

References 53 publications

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“…However, this is in sharp contrast to the results of Tohse et al [20] who did not observe a significant reduction in the response to phorbol esters in the same preparation, and to the augmentation observed in the response to phorbol myristate in rabbit atria1 myocytes [23]. In addition, in hippocampal neurons, high concentrations of phorbol dibutyrate do not affect IA [24]. Here, blockade of the A-current by arachidonic acid in bullfrog sympathetic neurons is described.…”

Section: Modulationcontrasting

confidence: 70%

Suppression of neuronal potassium A‐current by arachidonic acid

Villarroel

1993

FEBS Letters

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The effect of arachidonic acid on the A current (IA) has been studied in dissociated bullfrog neurons under whole-cell voltage-clamp conditions. Arachidonic acid reduced IA in a dose-dependent and reversible manner without a shift in the prepulse inactivation voltage-current relation. 1.75 PM inhibited IA by 50%, and higher concentrations caused a total suppression. In addition, arachidonic acid increased the M-current (I,), a different potassium current that does not inactivate. Neither indomethacin nor nordihydroguaiaretic acid, cyclooxygenase and lipoxygenase inhibitors respectively, prevented IA reduction. In contrast, nordihydroguaiaretic acid prevented Z, enhancement. Eicosatetraynoic acid, an arachidonic acid analog that cannot be metabolized, also reduced IA. These results suggest that arachidonic acid metabolism is not required to suppress IA.

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Section: Modulationcontrasting

confidence: 70%

Suppression of neuronal potassium A‐current by arachidonic acid

Villarroel

1993

FEBS Letters

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“…However, in our experiments, this mechanism does not seem to be involved, since H-89, a specific PKA inhibitor, neither mimicked nor blocked the effect of CCPA. On the other hand, stimulation of G o proteins by AD might activate the phospholipase C-PKC pathway, leading in this case to a decrease in Ca 2 þ current, as was observed in isolated hippocampal neurons and dorsal root ganglion neurons (Doerner et al, 1988;Rane et al, 1989). Application of H7, a PKC blocker, did not reverse the presynaptic inhibition induced by CCPA, and did not by itself modify basal mepp frequency.…”

Section: S De Lorenzo Et Almentioning

confidence: 79%

Presynaptic inhibition of spontaneous acetylcholine release induced by adenosine at the mouse neuromuscular junction

Lorenzo

Veggetti

Muchnik

et al. 2004

British J Pharmacology

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1 At the mouse neuromuscular junction, adenosine (AD) and the A 1 agonist 2-chloro-N 6 -cyclopentyl-adenosine (CCPA) induce presynaptic inhibition of spontaneous acetylcholine (ACh) release by activation of A 1 AD receptors through a mechanism that is still unknown. To evaluate whether the inhibition is mediated by modulation of the voltage-dependent calcium channels (VDCCs) associated with tonic secretion (L-and N-type VDCCs), we measured the miniature endplate potential (mepp) frequency in mouse diaphragm muscles. 2 Blockade of VDCCs by Cd 2 þ prevented the effect of the CCPA. Nitrendipine (an L-type VDCC antagonist) but not o-conotoxin GVIA (an N-type VDCC antagonist) blocked the action of CCPA, suggesting that the decrease in spontaneous mepp frequency by CCPA is associated with an action on L-type VDCCs only. 3 As A 1 receptors are coupled to a G i/o protein, we investigated whether the inhibition of PKA or the activation of PKC is involved in the presynaptic inhibition mechanism. Neither N-(2[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide (H-89, a PKA inhibitor), nor 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H-7, a PKC antagonist), nor phorbol 12-myristate 13-acetate (PHA, a PKC activator) modified CCPA-induced presynaptic inhibition, suggesting that these second messenger pathways are not involved. 4 The effect of CCPA was eliminated by the calmodulin antagonist N-(6-aminohexil)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) and by ethylene glycol-bis(b-aminoethyl ether)-N,N,N 0 ,N 0 -tetraacetic acid-acetoxymethyl ester e6TD-BM, which suggests that the action of CCPA to modulate L-type VDCCs may involve Ca 2 þ -calmodulin. 5 To investigate the action of CCPA on diverse degrees of nerve terminal depolarization, we studied its effect at different external K þ concentrations. The effect of CCPA on ACh secretion evoked by 10 mM K þ was prevented by the P/Q-type VDCC antagonist o-agatoxin IVA. 6 CCPA failed to inhibit the increases in mepp frequency evoked by 15 and 20 mM K þ . We demonstrated that, at high K þ concentrations, endogenous AD occupies A1 receptors, impairing the action of CCPA, since incubation with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, an A 1 receptor antagonist) and adenosine deaminase (ADA), which degrades AD into the inactive metabolite inosine, increased mepp frequency compared with that obtained in 15 and 20 mM K þ in the absence of the drugs. Moreover, CCPA was able to induce presynaptic inhibition in the presence of ADA. It is concluded that, at high K þ concentrations, the activation of A 1 receptors by endogenous AD prevents excessive neurotransmitter release.

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“…In our simulations, the depolarization at the subsynaptic membrane due to a postsynaptic train of fast somatic sodium action potentials was not sufficient, when paired with a weak presynaptic stimulus, to induce LTP. However, the results were quite different when a uniform density of low-threshold dendritic Ca2+ channels (41) was included in the model. Under these conditions, fast somatic action potentials activated the slower dendritic Ca2+ currents.…”

Section: Modelmentioning

confidence: 84%

Biophysical model of a Hebbian synapse.

Zador

Koch

Brown

1990

Proc. Natl. Acad. Sci. U.S.A.

212

126

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We present a biophysical model of electrical and Ca2' dynamics following activation of N-methyl-Daspartate (NMDA) receptors located on a dendritic spine. The model accounts for much of the phenomenology of the induction of long-term potentiation at a Hebbian synapse in hippocampal region CAI. (12,13). This increase is thought to be mediated by Ca>2 influx through the N-methyl-D-aspartate (NMDA) receptor-gated channel (13,14). Because the channel requires both ligand binding and postsynaptic depolarization for activation, it is ideally suited to contribute to the interactive requirement (4) for a Hebbian synapse.We have been interested in the role of the dendritic spine in LTP induction (9,11,15) and have constructed a biophysical model of electrical and Ca>2 dynamics in a spine after activation of NMDA receptors. Computer simulations indicate that the model can account for much of the known phenomenology of LTP induction at a Hebbian synapse in the CA1 region of the hippocampus. The results suggest that the microphysiology of the spine plays a critical role in the induction of this form of LTP. MODELThe biophysical mechanism of LTP induction has been best studied at the Schaffer collateral/commissural inputs to pyramidal cells of the CA1 region of the rodent hippocampus in the in vitro brain slice preparation. At least two pharmacologically distinguishable receptors mediate the excitatory postsynaptic response in this system. NMDA receptors mediate a slow current (16) with a substantial Ca2" component. The associated channel is voltage-dependent due to block byMg2`that is relieved by membrane depolarization (17-19).Non-NMDA receptors mediate a more rapid current with a negligible Ca`component.We simulated Ca`influx, transport, and buffering following activation of NMDA receptor-gated channels located on a spine head. The model (Fig. 1) consisted of separate electrical and Ca2+ components (15). The equations describing electrical and chemical dynamics were advanced independently and at the end of each time step electrical current was converted to ionic flux through Faraday's constant. These equations were discretized and then solved using alternating implicit-explicit steps (20, 21). Spine and Synapse. Total synaptic current (Fig. 1) was the sum of separate NMDA and non-NMDA components. An alpha function (22), I(t) = (Esyn -Vm) Kgpt exp(-t/tp), [1] was used for the non-NMDA current, with K = e/tp, e the base of the natural logarithm, tp = 1.5 msec, Esyn = 0 mV, and the peak conductance gp = 0.5 nS (9,23 tTo whom reprint requests should be addressed. 6718The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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

Cited by 157 publications

References 53 publications

Suppression of neuronal potassium A‐current by arachidonic acid

Suppression of neuronal potassium A‐current by arachidonic acid

Presynaptic inhibition of spontaneous acetylcholine release induced by adenosine at the mouse neuromuscular junction

Biophysical model of a Hebbian synapse.

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