Phasic secretion of acetylcholine at a mammalian neuromuscular junction.

Abstract

SUMMARY1. The transient increase in secretion of quanta of acetylcholine (phasic secretion) produced by an action potential or brief depolarizing current pulse in mouse phrenic nerve terminals was examined.2. Following an activating stimulus, there was a brief delay (minimum latency) followed by a sigmoidal increase in secretion which then decayed exponentially.3. The minimum latency, rise time and rate of decay of phasic secretion, whether elicited by action potentials or electrotonic depolarization, were all extremely sensitive to temperature, with Q10s as high as 4 at temperatures of 5-15 'C. Arrhenius plots of results showed a change in slope with temperature, the change appearing most marked at 20-25 0C.4. Phasic secretion in response to action potentials prolonged by inhibitors of K conductance (4-aminopyridine, uranyl, tetraethylammonium or Zn ions) showed an increase in minimum latency but no other change in time course.5. Depolarizing pulses of varying width (0.2-2 msec) applied to nerve terminals (in the presence of tetrodotoxin and 4-aminopyridine) affected minimum latency, but had no great effect on the time course of phasic secretion.6. Neither an increase in extracellular K ion concentration nor a decrease in pH had any effect on the time course of phasic secretion nor was any change produced by ethanol or octanol.7. Variations in extracellular Ca concentration, substitution of Sr ions for Ca ions and repetitive stimulation, while producing changes in the magnitude of secretion, produced no change in the time course of phasic secretion.

Analysis of Presynaptic Ca2+ Influx and Transmitter Release Kinetics during Facilitation at the Inhibitor of the Crayfish Neuromuscular Junction

“…5C, arrow). Similar to previous studies (Datyner and Gage, 1980;Parnas et al, 1989), the synaptic delay of facilitated IPSC did not change (Fig. 5C, inset, solid line).…”

“…These models also predict a small change in release kinetics during facilitation, although the change was considered too small to be detectable. These predictions are consistent with experimental work that has uncovered no change in release kinetics during facilitation (Datyner and Gage, 1980;Parnas et al, 1989).…”

“…We observed an increase in synaptic delay as the action potential duration lengthened. Such an increase has been shown in other preparations (Datyner and Gage, 1980;Sabatini and Regehr, 1996), although the underlying cause was not addressed. The time window relevant to synaptic delay should be the brief period after the peak of an action potential.…”

“…Augmentation is associated with an increase in hypertonic shock-induced release (Stevens and Wesseling, 1999). Finally, an increase in action potential duration can lengthen synaptic delay (Datyner and Gage, 1980;Sabatini and Regehr, 1996). Although the mechanisms underlying such changes in release kinetics may differ, these observations suggest that the secretion process could be an important site for modulating synaptic strength.…”

“…If this hypothesis is correct, how could one explain the facilitation observed with narrow spikes in which there is an increase in amplitude but not synaptic delay of postsynaptic responses (Datyner and Gage, 1980;Parnas et al, 1989) (Fig. 5)?…”