Sr²⁺‐dependent asynchronous evoked transmission at rat striatal inhibitory synapses in vitro

Abstract

In all preparations studied, a characteristic distinction of Sr¥versus Ca¥-mediated synaptic transmission is a reduced early (or phasic) component and an augmented late (or asynchronous) tail of individual miniature-like events called 'late release'. Thus, transmission in Sr¥ is desynchronized with respect to the normal situation. Understanding this non-physiological phenomenon may entail important insights into the mechanisms which under physiological conditions control the kinetics of evoked transmitter release. Thus, have proposed that preferential activation by Sr¥ of late, asynchronous release is due to binding at a secondary, highaffinity divalent cation binding site, where the action of Sr¥ is stronger than that of Ca¥. A high-affinity site in addition to the putative low-affinity receptor involved in synchronous release (cf. Heidelberger et al. 1994) has also been postulated in order to account for use-dependent synaptic facilitation (Yamada & Zucker, 1992). The twobinding-site hypothesis has gained indirect support from experiments on excitatory synapses lacking the presynaptic Ca¥-binding protein synaptotagmin I, where phasic release was suppressed and asynchronous release was intact or increased (Geppert et al. 1994). Alternatively, it has been suggested that a single releaseinducing binding site may suffice to explain Sr¥-induced late release if buffering, extrusion or sequestration are assumed to be less efficient for Sr¥ than for Ca¥ so that free Sr¥ concentration remains elevated for longer times

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.…”

Altered Localization of GABAAReceptor Subunits on Dentate Granule Cell Dendrites Influences Tonic and Phasic Inhibition in a Mouse Model of Epilepsy

“…This unexpected alteration in ␥2 localization led us to compare dendritic phasic inhibition of pilocarpine and control animals by eliciting an asynchronous release of GABA by local stimulation of axon terminals in the molecular layer in the presence of Sr 2ϩ . Because the asynchronous release under these conditions occurs only from the stimulated terminals (Oliet et al, 1996;Morishita and Alger, 1997;Rumpel and Behrends, 1999), the method revealed a significant decrease in dendritic synaptic inhibition of granule cells from pilocarpine-treated animals. This finding is consistent with a decrease in ␥2 subunit-containing receptors directly at synaptic contacts, because the ␥2 subunit is normally incorporated in most synaptic GABA A Rs (Somogyi et al, 1996;Sassoè-Pognetto et al, 2000).…”

“…However, measurement of dendritic synaptic inhibition is difficult in granule cells because in these neurons, most, if not all, sIPSCs originate from synapses close to the soma (Soltesz et al, 1995). To investigate the properties of inhibitory synapses in the dendrites of granule cells, we resorted to a technique measuring the asynchronous release of transmitter from stimulated nerve terminals when extracellular Ca 2ϩ is replaced with equimolar Sr 2ϩ (Oliet et al, 1996;Morishita and Alger, 1997;Rumpel and Behrends, 1999). Stimulating the dendritic GABAergic afferents in the presence of Sr 2ϩ , asynchronous IPSCs could be evoked in granule cells of both control and pilocarpine-treated animals (Fig.…”

Post‐tetanic potentiation of GABAergic IPSCs in cultured rat hippocampal neurones

“…Asynchronous transmitter release is blocked by EGTA AM at both excitatory (Cummings et al 1996) and inhibitory synapses (Rumpel & Behrends, 1999) and therefore probably requires diffusion of Ca¥ through the cytosol. This contrasts with synchronous release which is usually unaffected by EGTA AM, partly because the Ca¥ channels are thought to be in close association with the docked vesicles Mochida et al 1996), and the binding rate of Ca¥ by EGTA is much slower than that by the vesicle-associated Ca¥ sensor.…”