Strontium and quantal release of transmitter at the neuromuscular junction

Abstract

SUMMARY1. Previous work has shown that in calcium-free solutions nerve impulses invade the motor nerve terminals at the neuromuscular junction, but fail to release transmitter. In these conditions, strontium ions applied iontophoretically to a minute part of a junction, or to the whole muscle by bath application, restore to the nerve impulse its ability to release transmitter.2. As with calcium, the transmitter released in the presence of strontium is in the form of packages (quanta) whose release can be predicted from Poisson's Theorem.3. The mean number of quanta released by a nerve impulse increases with the concentration of strontium. Strontium is much less effective than calcium in equimolar concentrations.4. Transmitter quanta released in the presence of strontium evoke larger unit potentials than quanta released in the presence of calcium. The larger size of the Sr-unit potentials is caused by a prolongation of transmitter action, presumably due to a post-synaptic effect of strontium.5. Neuromuscular transmission was blocked in some fibres when the concentration of strontium was raised beyond 10 mm. This junctional block was presumably due to a failure in the propagation of nerve impulses.6. The post-stimulation increase in the frequency of miniature end-plate potentials, which is normally seen in calcium solutions, is also observed when calcium is substituted by strontium. The post-stimulation effect increases with the concentration of strontium.

Decreased Frequency But Not Amplitude of Quantal Synaptic Responses Associated with Expression of Corticostriatal Long-Term Depression

“…Furthermore, the mode of action of Sr 2ϩ is qualitatively similar to that of Ca 2ϩ , such that Sr 2ϩ substitution does not appear to change the minimal synaptic delay in response to nerve stimulation or the standard cooperativity of transmitter release (Miledi, 1966;Meiri and Rahamimoff, 1971). However, Sr 2ϩ reduces the efficacy of a fast, synchronous component of release and greatly facilitates a slow, asynchronous component of release, which has been shown to be quantal (Dodge et al, 1969). Recently, these observations at the neuromuscular junction have been reproduced in hippocampal cultures and slices (Goda and Stevens, 1996;Oliet et al, 1996).…”

Cations Residing at the Selectivity Filter of the Voltage-Gated Ca2+-Channel Modify Fusion-Pore Kinetics

“…Sr 2+ and Ba 2+ can effectively substitute for Ca 2+ in driving synaptic transmission. 6,[25][26][27][28][29] Once vesicle fusion occurs with the pre-synaptic membrane, the continuation of the fusion process is mainly regulated by factors unrelated to its initiation. Since amperometric spikes represent the collapse of single vesicles, substituting the charge carrier would not be expected to lead to large changes in spikes kinetics.…”

Direct Measurement of AMPA Receptor Desensitization Induced by Glutamatergic Synaptic Transmission

“…According to the quantal hypothesis, such depression would be reflected in a reduction in the size of the mEPSC (Magleby and Palotta, 1981). We tested for depression of quantal size by eliciting eEPSCs in a Sr 2ϩ -containing extracellular solution, which increases the probability that single transmitter vesicles are released from the stimulated synapse for a short period after the eEPSC (Dodge et al, 1969;Goda and Stevens, 1994). To ensure that this manipulation had no pre-or postsynaptic effects that enhanced desensitization, we elicited pairs of eEPSCs to test for an effect of Sr 2ϩ on pairedpulse synaptic depression, or PPD (amplitude of the second eEPSC/amplitude of the first eEPSC ϫ 100).…”