The modulation of neurotransmitter release at synaptic junctions

Erulkar, S. D.

doi:10.1007/bfb0033867

Cited by 34 publications

(21 citation statements)

References 418 publications

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“…The order of inhibition potency was w-agatoxin IVA (IC50, 5 nM) > wconotoxin MVIIC t sFTX (IC50, 2000 FM). The inhibitions were reversible, surmountable by conditions that facilitate Caa2+ influx and very much like that produced by a deficiency of Ca2+ (Mallart & Martin, 1968;Erulkar, 1983 (Luebke, Dunlap & Turner, 1993;Takahashi & Momiyama, 1993;Turner, Adams & Dunlap, 1993;Regehr & Mintz, 1994). w)-Conotoxin GVIA, an N-type channel blocker, inhibits ACh release slightly at high concentrations (Hong, Tsuji & Chang, 1992).…”

Section: Discussionmentioning

confidence: 94%

Inhibition of acetylcholine release from mouse motor nerve by a P‐type calcium channel blocker, omega‐agatoxin IVA.

Hong

Chang

1995

The Journal of Physiology

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1. The effects were studied of the central neurone P-type Ca2+ channel blockers, w-agatoxin IVA, w-conotoxin MVIIC (polypeptide toxins) and synthetic funnel-web spider polyamine toxin on acetylcholine release from mouse motor nerve. 2. o-Agatoxin IVA decreased the quantal content of endplate potentials and blocked synaptic transmission in the nanomolar range in a reversible manner, whereas the other toxins depressed transmission in the hundred micromolar range. 3. The polyamine toxin, but not the polypeptide toxins, decreased the amplitude of the miniature endplate potential. The increase in the frequency of miniature endplate potentials evoked by high [K+], but not that evoked by a-latrotoxin, was effectively antagonized by wi-agatoxin IVA. 4. In the presence of w-agatoxin IVA, high frequency nerve stimulation produced facilitation of endplate currents and tetanic contractions.5. The results suggest that, under physiological conditions, the Ca2+ necessary for nerve action potential-evoked acetylcholine release is translocated via a subtype of the P-type Ca2+ channel sensitive to w-agatoxin IVA.The biochemical event of neurotransmitter release is initiated by an elevation of intraterminal Ca2c oncentration resulting from rapid Ca2+ influx through voltage-gated Ca2+ channels (Llina's, Steinberg & Walton, 1981). However, differences in channel proteins and dynamic interactions with lipid matrices endow Ca2+ channels with heterologous electrophysiological and pharmacological characteristics. In mammalian neuromuscular junctions the evoked release of acetylcholine (ACh) is resistant to w)-conotoxin GVIA and 1,4-dihydropyridine Ca2+ modulators, which affect N-and L-type Ca2+ channels and neurotransmission in a variety of other neurones (Kerr & Yoshikami, 1984;Sano, Enomoto & Maeno, 1987;Atchison, 1989;Hess, 1990 (Llinas, Sugimori, Hillman & Cherksey, 1992). We compared the effects of three P-channel blockers and a glutamate receptor-channel antagonist on synaptic transmission in a peripheral motor nerve, including the polypeptide toxins w-agatoxin IVA (Mintz, Adams & Bean, 1992) and w-conotoxin MVIIC (Hillyard et al. 1992) and a synthetic funnel-web spider polyamine toxin (sFTX) and argiotoxin. (Argiotoxin is a polyamine from the spider Argiope lobata that retains the sFTX moiety and blocks a glutamate-gated channel; Priestley, Woodruff & Kemp, 1989.) The results indicate that w-agatoxin IVA is a more potent and specific blocker than other toxins and suggest that a subtype of the P-type channel is involved in physiological release of ACh. METHODSNerve-muscle preparation Phrenic nerve hemidiaphragms were isolated from mice (ICR strain,(20)(21)(22)(23)(24)(25)). Mice were killed by a blow to the head followed by exsanguination. Preparations were bathed in Tyrode solution (composition (mM): NaCl, 137; KCl, 2-8; CaCl2, 1.8; MgCl2, 1P1; NaHCO3, 11; NaH2PO4, 0 33; and glucose,

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Section: Discussionmentioning

confidence: 94%

Inhibition of acetylcholine release from mouse motor nerve by a P‐type calcium channel blocker, omega‐agatoxin IVA.

Hong

Chang

1995

The Journal of Physiology

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“…When the LOT of slices of olfactory cortex are stimulated twice in rapid succession, the response evoked by the second test stimulus is greater than that evoked by the first conditioning stimulus (Richards, 1972;Bower & Haberly, 1986). Such synaptic facilitation occurs at a number of sites in the CNS (Andersen, 1960a, b;Eccles et al, 1961; Kuno & Weakly, 1972;Erulker, 1983) and is usually considered to reflect a presynaptic phenomenon involving an increase in transmitter release caused by the persistence of calcium activity triggered by the conditioning stimulus (Katz & Miledi, 1968). However, when transmitter release is high there is a simultaneous underlying reduction in the response to the test stimulus probably caused by depletion of transmitter stores by the conditioning pulse.…”

Section: Introductionmentioning

confidence: 99%

Possible presynaptic actions of 2‐amino‐4‐phosphonobutyrate in rat olfactory cortex

Anson

Collins

1987

British J Pharmacology

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1 The effect of 2-amino-4-phosphonobutyrate (APB) on facilitation at the lateral olfactory tract (LOT)-superficial pyramidal cell synapse of the olfactory cortex has been studied by recording the relative changes in amplitude of the N-waves evoked on stimulation of the LOT by pairs of stimuli. 2 Although APB (0.01 to 5 mM) reduced the amplitude of the conditioning response there was an overall increase in facilitation over conditioning intervals of up to 1700 ms which was concentrationdependent and inversely related to the concentration of extracellular calcium (1.25 to 5 mM). 3 The L-(+ )-isomer ofAPB was more potent than the D-(-)-form in increasing synaptic facilitation. 4 The potassium channel blockers 4-aminopyridine (0.25mM), 3,4-diaminopyridine (0.1mM), tetraethylammonium (10 mM) and catechol (1 mM) all reduced facilitation but failed to antagonize the increase in facilitation produced by APB (I mM). In contrast, all 4 drugs antagonized APB-induced reductions in the amplitude of the conditioning response. 5 APB (1 mM) significantly reduced the K+-evoked release of endogenous aspartate and glutamate but not of y-aminobutryic acid from slices of olfactory cortex. 6 It is suggested that APB reduces the amplitude of the conditioning response and increases synaptic facilitation by reducing transmitter release from the LOT terminals. The mechanism is unlikely to involve activation of terminal potassium currents.

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“…1), is not a constant process. Rather it is subject to stochastic fluctuations (2,3), periodic oscillations (4,5), and intrinsic and extrinsic modulation (6)(7)(8)(9). A growing body of evidence suggests that much of the flexibility in synaptic function is achieved by phosphorylation and dephosphorylation of key protein molecules (10)(11)(12).…”

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confidence: 99%

Protein phosphatase inhibitor okadaic acid enhances transmitter release at neuromuscular junctions.

Abdul‐Ghani¹,

Kravitz²,

Meiri³

et al. 1991

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

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To test the hypothesis that continual phosphorylation and dephosphorylation of protein components of nerve terminals might be important determinants of synaptic efficacy, the effect of okadaic acid, a potent natural inhibitor of two serine threonine protein phosphatases (phosphatase 1 and phosphatase 2A), was examined on synaptic transmission at frog (cholinergic) and lobster (glutamatergic and GABAergic) neuromuscular junctions. At frog junctions, the addition of 1 ,uM okadaic acid to the extracellular fluid caused almost a doubling of the amplitude of the end-plate potential. The effect of okadaic acid was reversible. Quantal analysis showed that the augmenting effect was presynaptic, resulting from an increase in the number of quanta of transmitter released by a nerve impulse. There was no significant change in the amplitude of spontaneously liberated miniature end-plate potentials, but their frequency of release increased in parallel with the increase in amplitude of the nerve-evoked synaptic potential. Similar studies with lobster neuromuscularjunctions showed increases in the size of both excitatory and inhibitory synaptic responses that were similar in magnitude to the effects seen in the frog junctions. No significant changes in membrane potential or in input resistance accompanied the increased response size. These results suggest that transmitter release at a variety of junctions using different transmitters is constantly modulated by phosphorylation and dephosphorylation of important protein components within nerve terminals.Synaptic transmission, the process by which a presynaptic nerve terminal releases transmitter and the postsynaptic cell detects it (cf. ref. 1), is not a constant process. Rather it is subject to stochastic fluctuations (2, 3), periodic oscillations (4, 5), and intrinsic and extrinsic modulation (6-9). A growing body of evidence suggests that much of the flexibility in synaptic function is achieved by phosphorylation and dephosphorylation of key protein molecules (10-12).In this paper, we examine whether inhibiting the removal of phosphate groups from proteins alters normal synaptic transmission. For this purpose we employ the dinoflagellate toxin okadaic acid (13,14). This toxin, which is responsible for diarrhetic shellfish poisoning (14, 15), inhibits two of the four major serine and threonine cytosolic protein phosphatases (protein phosphatase 1 and protein phosphatase 2A) in all species tested (16). Since okadaic acid is lipid soluble, it readily penetrates cells and is applied to potential targets by dissolving it in the fluid bathing the tissues. In these studies we explore the hypothesis that proteins important for synaptic function normally cycle between different activity states determined by their rates of phosphorylation and dephosphorylation and that removal of phosphate groups requires at least one of the phosphatases inhibited by okadaic acid. Treatment with okadaic acid should then trap these proteins in their phosphorylated forms, which might be reflected ...

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The modulation of neurotransmitter release at synaptic junctions

Cited by 34 publications

References 418 publications

Inhibition of acetylcholine release from mouse motor nerve by a P‐type calcium channel blocker, omega‐agatoxin IVA.

Inhibition of acetylcholine release from mouse motor nerve by a P‐type calcium channel blocker, omega‐agatoxin IVA.

Possible presynaptic actions of 2‐amino‐4‐phosphonobutyrate in rat olfactory cortex

Protein phosphatase inhibitor okadaic acid enhances transmitter release at neuromuscular junctions.

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