Probabilistic secretion of quanta from nerve terminals in toad (Bufo marinus) muscle modulated by adenosine.

SUMMARY1. Endogenous adenosine, which is produced by enzymatic degradation of ATP released from synaptic vesicles, has been shown to be a potent inhibitor of acetylcholine release from motor nerve terminals. It has been proposed that this auto-inhibition mechanism might contribute significantly to tetanic stimulationinduced depression.2. Levels of facilitation and depression during a 20 Hz stimulus train differ greatly in different terminals, but are strongly and non-linearly correlated with the terminal's release characteristics (the amount of transmitter released per unit terminal length, or 'release efficacy'). There is a weaker, approximately linear, correlation between depression and release efficacy at 2 Hz stimulation.3. The effects of both endogenous and exogenously applied adenosine are also highly variable for different nerve terminals. We have shown that much of this variability can be attributed to the release efficacy of each terminal in the case of endogenous effects, and to the size of the nerve terminal in the case of exogenously applied adenosine receptor agonists.4. When nerve terminals are pooled according to their individual release characteristics, endogenous adenosine can be shown to contribute significantly to stimulation-induced depression of release primarily in terminals that release enough transmitter to generate significant levels of adenosine, but do not release so much transmitter that depletion of releasable quanta is severe.

Section: Effects Of Endogenous Adenosinementioning

confidence: 98%

Endogenous adenosine modulates stimulation‐induced depression at the frog neuromuscular junction.

Meriney¹,

Grinnell²

1991

“…At motor nerve endings, adenosine derivatives are released together with ACh (Silinsky, 1975;Smith & Lu, 1991) and act via adenosine receptors at the extracellular surface of the nerve ending as negative feedback modulators of ACh release (Ginsborg & Hirst, 1972; Silinsky, 1980;Ribeiro & Sebastiaa, 1987; Bennett, Karunanithi & Lavidis, 1991). Despite the suggestions that adenosine derivatives may be responsible for presynaptic neuromuscular depression (Silinsky, 1975;Meriney & Grinnell, 1991), the specific target site for the inhibitory effect of adenosine on transmitter release is controversial.…”

Section: Introductionmentioning

confidence: 99%

Calcium currents at motor nerve endings: absence of effects of adenosine receptor agonists in the frog.

Silinsky

Solsona

1992

SUMMARY1. The effects of adenosine (50 fIM) and 2-chloroadenosine (1-25 /M) were studied on Ca2+ currents in frog motor nerve endings.2. Ca2+ currents associated with the synchronous, neurally evoked release of acetylcholine (ACh) were measured using either perineural or patch recording methods. Tetraethylammonium and/or 3,4-diaminopyridine were employed to block K+ currents.3. Ca2+ currents were depressed by wo-conotoxin (1-5-2-5 gM), Cd21 (100 fM-2 mM), Co2+ (500 /M-5 mM) or by a reduction of the extracellular calcium concentration. Such currents were also observed when Sr2+ was substituted for Ca2+. Both ACh release and Ca2+ currents at motor nerve endings have been reported to be insensitive to 1,4-dihydropyridine antagonists in this species.4. Adenosine receptor agonists did not affect Ca2+ currents at concentrations that produced maximal inhibition of ACh release. 5. The effects of adenosine receptor agonists were examined on asynchronous K+-dependent ACh release under conditions in which the Ca2+ concentration gradient is likely to be reversed (Ca2+-free Ringer solution containing 1 mm EGTA). ACh release was measured by monitoring the frequency of occurrence of miniature endplate potentials (MEPPs). In Ca2+-free solutions containing 1 mm EGTA, high K+ depolarization caused a decrease in MEPP frequency, presumably because it elicits the efflux of Ca2+ from the nerve ending via membrane Ca2+channels in a reverse Ca2+

“…However, a recent theoretical analysis has shown that such non-uniformity does not reduce the variance of secretion so that binomial statistics apply; rather the process could be explained if a co-transmitter is released with the acetylcholine quantum following a nerve impulse and this co-transmitter then acts on the terminal to inhibit secretion from adjacent release sites (Bennett & Robinson, 1990). In a previous paper (Bennett, Karunanithi & Lavidis, 1991) it was shown that a candidate for this autoinhibitory process is adenosine, either derived from the secretion of its nucleotide triphosphate (ATP) or directly from endogenous stores at the synaptic site (Sebastiao & Ribeiro, 1985;Ribeiro & Sebastiao, 1987; for a review see Ribeiro & Sebastiao, 1986). Adenosine decreases quantal secretion at neuromuscular synapses (Ginsborg & Hirst, 1972;Silinksy, 1984; for a review see Jones, 1987) and decreases the variance of the secretion (Bennett et al 1991) before being inactivated by uptake (Ribeiro & Sebastiao, 1987).…”

Section: Introductionmentioning

confidence: 99%

“…In a previous paper (Bennett, Karunanithi & Lavidis, 1991) it was shown that a candidate for this autoinhibitory process is adenosine, either derived from the secretion of its nucleotide triphosphate (ATP) or directly from endogenous stores at the synaptic site (Sebastiao & Ribeiro, 1985;Ribeiro & Sebastiao, 1987; for a review see Ribeiro & Sebastiao, 1986). Adenosine decreases quantal secretion at neuromuscular synapses (Ginsborg & Hirst, 1972;Silinksy, 1984; for a review see Jones, 1987) and decreases the variance of the secretion (Bennett et al 1991) before being inactivated by uptake (Ribeiro & Sebastiao, 1987). The question arises as to how adenosine exerts its effects at synapses which secrete acetylcholine.…”

Section: Introductionmentioning

confidence: 99%

Probabilistic secretion of quanta from nerve terminals in avian ciliary ganglia modulated by adenosine.

Bennett

1991

Self Cite

SUMMARY1. The effects of adenosine on the probability of secretion of acetylcholine quanta and on presynaptic and postsynaptic action potentials was examined in the posthatched avian ciliary ganglion.2. Adenosine (20 /tM) reduced the average size of the excitatory postsynaptic potential (EPSP) by 33 %. This was due to a decrease in quantal content of the EPSP (mn). The effect was blocked by theophylline (50 /IM). 4. Plateau-type action potentials with a large calcium component were generated in the ciliary neurones by bathing the ganglion in tetraethylammonium ions (TEA, 10 mM). Adenosine (20 IiM) reduced the duration of these action potentials on short exposures (< 20 min) but increased the duration on longer exposure (> 30 min).Adenosine did not affect the normal action potentiat recorded in the absence of TEA.5. Adenosine (20 ftM) hyperpolarized the nerve terminal and as a consequence increased the size of the presynaptic action potential and reduced its afterhyperpolarization. 6. Plateau-type action potentials with a large calcium component were generated in the nerve terminals using TEA (10 mM). The duration of these action potentials was significantly reduced by adenosine (20 /tM).7. Adenosines action on nerve terminals, to hyperpolarize the membrane and reduce calcium influx, may contribute to its effect in reducing m of the EPSP.