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Results for “Presynaptic Terminals”

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PubMed1996

A voltage-dependent and calcium-permeable ion channel in fused presynaptic terminals of Torpedo.

1. We used a preparation of fused presynaptic nerve terminals of Torpedo electromotor nerve and the patch-clamp technique for characterization of single ion channels. We report here of a large, nonselective ion channel which is highly voltage dependent. 2. The slope conductance of the I-V relation was estimated by either direct measurement of the single-channel current amplitude at different voltages (850 +/- 18 pS (SE); n = 9) or by variance analysis (834 +/- 23 pS; n = 5). 3. The voltage dependence was examined in three ways. At steady-state DC voltage conditions, NPo (the open probability times the number of channels in the patch) was estimated. At potentials < 0 mV, the probability of the channel to open is negligible and increases dramatically, within a very narrow voltage range, to > 50% at +8 mV (n = 8). 4. In pulse experiments, the activation time delay is shorter as the voltage step reaches more positive values. The mean time for half activation (T1/2) decreases from 15 ms at +10 mV to 4 ms at +30 mV (n = 5). 5. Ensemble currents exhibit rectification in response to voltage ramps at negative potentials (n = 10). 6. The channel was found to be nonselective. Its permeability to Na+, K+, Cl-, glutamate, Ba+2, and Ca+2, relative to Na+, was 1.00, 1.00, 1.22, 1.07, 0.85, and 0.62, respectively. 7. Based on the transport number of calcium, the calculated driving force, and the mean channel open time, we estimated the number of calcium ions entering the nerve terminal upon depolarization. This number is not substantially different from the number of ions entering through voltage-dependent, calcium-selective channels in other cells. 8. We speculate that this nonselective ion channel, may serve as a calcium entry route into the nerve terminal and hence be involved in transmitter release.

Animals↗

PubMed1993

Quantitative mapping of glutamate presynaptic terminals in the supraoptic nucleus and surrounding hypothalamus.

Although the hypothalamus is generally regarded to have low levels of glutamate receptors, anatomical and physiological studies have provided consistent evidence implicating glutamate as a potential transmitter for the control of neuroendocrine cell activity. To clarify the extent of the contribution of synapses utilizing glutamate for control of vasopressin/oxytocin neuroendocrine cells, we mapped the density and location of glutamate immunoreactive terminals in the supraoptic nucleus and surrounding hypothalamus. Colloidal gold particle densities in presynaptic terminals were measured from electron micrographs of: (1) the magnocellular neuroendocrine cell perikarya (main body of the supraoptic nucleus), (2) the dendritic field of the magnocellular neuroendocrine cells (ventral dendritic neuropil) and (3) the hypothalamic perinuclear zone dorsal to the supraoptic nucleus. In addition, serial sections were stained, alternatively, for glutamate or GABA to determine glutamate staining in GABA cells. Terminals with high glutamate immunoreactivity were clearly distinguished from the glutamate precursor staining found in GABA terminals and were abundant at all rostral-caudal levels within each region. The number of glutamate terminals identified in each region was similar but represented a very high proportion of all terminals in the ventral dendritic neuropil (38%) vs. the main body of the supraoptic nucleus and the perinuclear zone (20-22%). The regional variation in the relative proportion of glutamate terminals was determined largely by differences in the number of non-glutamate terminals within each region. Glutamate and GABA terminals together accounted for over two-thirds of the innervation of vasopressin/oxytocin neuroendocrine cells. No systematic relationship was observed between excitatory and inhibitory inputs on the same cell. These results suggest that glutamate is the predominant excitatory transmitter used for control of vasopressin/oxytocin cells. The relative contribution of glutamate neurotransmission to a particular region will depend, in part, on the number and type of competing non-glutamate terminals.

Animals↗

PubMed1996

Inhibition of acetylcholine release from presynaptic terminals of skate electric organ by calcium channel antagonists: a detailed pharmacological study.

Release of acetylcholine (ACh) from the presynaptic terminals in skate electric organ was tested for its sensitivity to calcium channel antagonists. A pharmacological profile was established by measuring inhibition of K(+)-stimulated release of [3H]ACh from prelabelled tissue slices. Peptide antagonists of N-type (omega-conotoxins GVIA and MVIIA) and P-type (omega-agatoxin-IVA) channels had no effect, whereas both omega-conotoxins MVIIC and SVIB produced concentration-dependent inhibition and could completely block ACh release. omega-Conotoxin GVIA and omega-agatoxin IVA did not attenuate the block by omega-conotoxin MVIIC. The inorganic ions, Cd2+ and Ni2+, also produced a full inhibition of release (Cd2+ > > Ni2+) and Gd3+ a partial one. Drugs targeting L-type channels (diltiazem, nifedipine and verapamil) at low microM concentrations and a synthetic analogue of the polyamine toxin from funnel web spider venom (sFTX) at 1 mM were all non-inhibitory. Inhibition by omega-conotoxins MVIIC (IC50 25 nM) and SVIB (IC50 500 nM) was reversible and modulated by external concentrations of Ca2+. Inhibitory potency was increased by lowering and decreased by elevating external Ca2+. This "antagonistic" effect of Ca2+ was also seen with Cd2+ inhibition. The inhibitory potency of omega-conotoxin MVIIC was unaffected by predepolarisation. End plate potentials generated by release of endogenous ACh in electrically-stimulated slices were also reversibly blocked by Cd2+ and omega-conotoxins MVIIC and SVIB but were unaffected by omega-conotoxin GVIA and omega-agatoxin IVA. It is concluded that ACh release in skate electric organ depends on presynaptic calcium channels which have different pharmacological properties from established sub-types.

Acetylcholine↗

PubMed2000

Functional coupling of Ca(2+) channels to ryanodine receptors at presynaptic terminals. Amplification of exocytosis and plasticity.

Ca(2+)-induced Ca(2+) release (CICR) enhances a variety of cellular Ca(2+) signaling and functions. How CICR affects impulse-evoked transmitter release is unknown. At frog motor nerve terminals, repetitive Ca(2+) entries slowly prime and subsequently activate the mechanism of CICR via ryanodine receptors and asynchronous exocytosis of transmitters. Further Ca(2+) entry inactivates the CICR mechanism and the absence of Ca(2+) entry for >1 min results in its slow depriming. We now report here that the activation of this unique CICR markedly enhances impulse-evoked exocytosis of transmitter. The conditioning nerve stimulation (10-20 Hz, 2-10 min) that primes the CICR mechanism produced the marked enhancement of the amplitude and quantal content of end-plate potentials (EPPs) that decayed double exponentially with time constants of 1.85 and 10 min. The enhancement was blocked by inhibitors of ryanodine receptors and was accompanied by a slight prolongation of the peak times of EPP and the end-plate currents estimated from deconvolution of EPP. The conditioning nerve stimulation also enhanced single impulse- and tetanus-induced rises in intracellular Ca(2+) in the terminals with little change in time course. There was no change in the rate of growth of the amplitudes of EPPs in a short train after the conditioning stimulation. On the other hand, the augmentation and potentiation of EPP were enhanced, and then decreased in parallel with changes in intraterminal Ca(2+) during repetition of tetani. The results suggest that ryanodine receptors exist close to voltage-gated Ca(2+) channels in the presynaptic terminals and amplify the impulse-evoked exocytosis and its plasticity via CICR after Ca(2+)-dependent priming.

Animals↗

PubMed2001

Endogenous cannabinoid as a retrograde messenger from depolarized postsynaptic neurons to presynaptic terminals.

Cannabinoid receptors are the molecular targets for the active component Delta(9)-tetrahydrocannabinol of marijuana and hashish, and constitute a major family of G protein-coupled seven-transmembrane-domain receptors. They consist of type 1 (CB1) and type 2 (CB2) receptors of which the CB1 is rich in various regions of the CNS. Accumulated evidence suggests that endogenous cannabinoids function as diffusible and short-lived intercellular messengers that modulate synaptic transmission. Recent studies have provided strong experimental evidence that endogenous cannabinoids mediate signals retrogradely from depolarized postsynaptic neurons to presynaptic terminals to suppress subsequent neurotransmitter release, driving the synapse into an altered state. In hippocampal neurons, depolarization of postsynaptic neurons and resultant elevation of [Ca(2+)](i) lead to transient suppression of inhibitory transmitter release (depolarization-induced suppression of inhibition, DSI). In cerebellar Purkinje cells, on the other hand, depolarization-induced elevation of [Ca(2+)](i) causes transient suppression of excitatory transmitter release (depolarization-induced suppression of excitation, DSE). DSI and DSE appear to share the same properties and may be a general and important mechanism by which the postsynaptic neuronal activity can influence the amount of transmitter release.

Animals↗

PubMed1981

Uptake of horseradish peroxidase by presynaptic terminals of bipolar cells and photoreceptors of the from retina.

The uptake of horseradish peroxidase (HRP) into synaptic vesicles of presynaptic terminals in the inner and outer plexiform layers of isolated frog retinas was studies by electron microscopy. Uptake into the terminals of bipolar cells was found to be enhanced by exposure of the preparations to elevated concentrations of potassium ions, and by exposure to aspartic acid or glutamic acid. Glycine had much less effect on the terminals. These results suggest that HRP uptake may prove useful in monitoring some aspects of the responses of inner plexiform layer cells to conditions of physiological interest. Uptake into photoreceptor terminals was also enhanced by elevated potassium concentrations; the effects of the amino acids were complex.

Amino Acids↗

PubMed2001

Antenatal betamethasone treatment reduces synaptophysin immunoreactivity in presynaptic terminals in the fetal sheep brain.

Knowledge of morphofunctional effects on the fetal brain induced by exogenous glucocorticoids is limited. Recently, we reported alterations of both the neuronal cytoskeleton and electrocortical function in the ovine fetal brain after antenatal betamethasone treatment in doses used in perinatal medicine. In the present study we examined whether these changes are accompanied by morphological alterations of synapses. Chronically instrumented fetal sheep at 0.87 of gestation were treated either with isotonic saline (n=7) or 10 microg/h betamethasone (n=7) over 48 h administered directly to the fetal jugular vein. Paraffin sections of the frontal neocortex, caudate putamen and hippocampus were stained with a monoclonal antibody against synaptophysin, a specific membrane protein of presynaptic vesicles and quantified morphometrically. Synaptophysin-like immunoreactivity (synaptophysin-LI) showed a widespread granular pattern in the neuropil. Betamethasone exposure reduced synaptophysin-LI in the frontal neocortex, caudate putamen and hippocampus by 46.9, 41.0 and 55.4%, respectively, (P<0.05) that was not accompanied by irreversible neuronal damage. These results suggest that clinical doses of betamethasone have acute effects on presynaptic terminals in the fetal sheep brain that could contribute to the altered complexity of electrocortical function that we have shown previously to occur following fetal exposure to betamethasone.

Animals↗

PubMed1998

Patch-clamp recordings from cerebellar basket cell bodies and their presynaptic terminals reveal an asymmetric distribution of voltage-gated potassium channels.

Cerebellar basket cells form highly specialized inhibitory synaptic contacts with Purkinje cells, namely the pericellular basket and pinceau nerve terminal structures, wrapping around the Purkinje cell somatic and axon hillock regions. These inhibitory synaptic contacts are ideally located to control the ultimate output of the cerebellar cortex. Previous immunohistochemical studies have shown that these synaptic structures possess a very high density of the dendrotoxin (DTX)-sensitive potassium channel subunit, Kv1.2. We have taken advantage of this unique anatomical arrangement offering a high concentration of identified Kv channel subunits by combining whole-cell patch-clamp recording and fluorescence microscopy to establish a novel preparation and perform the first recordings from unambiguously identified mammalian CNS inhibitory presynaptic terminals. We report that DTX-sensitive potassium channels are present in basket cell terminals but not in the basket cell soma. This selective cellular distribution suggests that these channels play an important role in modulating cerebellar inhibitory synaptic transmission.

Animals↗

PubMed1990

[The structural correlations in the presynaptic terminals from the dorsal horn of the spinal cord].

The summarized data on three-dimensional parameters of ultrastructural elements of presynaptic terminals (PTs) in the dorsal horn of the cat spinal cord are presented. Interrelations of the following parameters were studied: mean volume and plasma membrane surface area of PTs; mean volume, surface area and number of mitochondria in the PTs; mean area and the number of active zones, mean number of synaptic vesicles per each observed PT. The data obtained were regarded as parameters reflecting the features of ion diffusion, transmitter release and vesicular recycling in PTs.

Animals↗

PubMed1992

Presynaptic terminal loss from alpha-motoneurones following the retrograde axonal transport of diphtheria toxin.

Intercostal motoneurones intoxicated following intraneural injection of diphtheria toxin exhibited a progressive dilatation and fragmentation of Nissl body rough endoplasmic reticulum (rER), coupled with two different forms of presynaptic terminal response. Firstly, terminal dysjunction without prior degeneration, and secondly, Wallerian-type degeneration. Dysjunction was attributed to a toxin-related failure by the motoneurones to maintain postsynaptic site structure. Degeneration was considered to arise from toxicity in presynaptic neurones, either neighbouring motoneurones or local interneurones. Morphometry revealed that by 8 days, intoxicated motoneurones exhibited a 33% loss in terminal frequency, a 15% loss in residual presynaptic membrane, and a 43% loss in overall presynaptic input. The concomitant loss of synaptic sites was greater that the overall loss of presynaptic membrane, indicating a toxin-related deficiency of the maintenance of postsynaptic sites. Analyses of the relationship between changes in terminal numbers and the development of Nissl body abnormality in the postsynaptic motoneurone identified three groups of motoneurones: (i) those with normal presynaptic input and normal neuronal Nissl body rER; (ii) those showing a dramatic loss of presynaptic input and a marked dilatation and fragmentation of Nissl bodies; and (iii) neurones exhibiting a maintained or further loss of presynaptic input coupled with extreme dilatation and fragmentation of Nissl body rER with loss of Nissl body structure. These changes are discussed in context with the known molecular action of diphtheria toxin.

Animals↗

PubMed1988

Phase-linked modulation of excitability of presynaptic terminals of low-threshold afferent fibers in the inferior alveolar nerve during cortically induced fictive mastication in the guinea pig.

Excitability of presynaptic terminals of low-threshold primary afferent fibers in the inferior alveolar nerve was tested in the trigeminal spinal nucleus of the ketamine-anesthetized, paralyzed guinea pig, by Wall's method. Fictive mastication was induced by repetitive stimulation of the cortical masticatory area, and was monitored by rhythmical burst activity in the jaw-opening anterior digastric motoneuron pool. The excitability was rhythmically modulated in a phase-linked manner during the masticatory cycle: it was decreased coincidentally with the digastric burst activity (jaw-opening phase) and increased during the middle and late periods of the interburst phase (jaw-closing phase) of the masticatory cycle. The results imply that presynaptic modulation of synaptic transmission of peripheral inputs from primary afferents to interneurons in the jaw-opening reflex pathway may contribute to the rhythmical modulation of the jaw-opening reflex evoked by innocuous stimulation of the intraoral structures during mastication; presynaptic inhibition contributing to the depression of the jaw-opening reflex during the jaw-closing phase and presynaptic facilitation to its enhancement during the jaw-opening phase.

Afferent Pathways↗

PubMed1999

Involvement of cGMP-dependent protein kinase in adrenergic potentiation of transmitter release from the calyx-type presynaptic terminal.

I have previously reported that norepinephrine (NE) induces a sustained potentiation of transmitter release in the chick ciliary ganglion through a mechanism pharmacologically distinct from any known adrenergic receptors. Here I report that the adrenergic potentiation of transmitter release was enhanced by a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX) and by zaprinast, an inhibitor of cGMP-selective phosphodiesterase. Exogenous application of the membrane-permeable cGMP, 8-bromo-cGMP (8Br-cGMP), potentiated the quantal transmitter release, and after potentiation, the addition of NE was no longer effective. On the other hand, 8Br-cAMP neither potentiated the transmitter release nor occluded the NE-induced potentiation. The NE-induced potentiation was blocked by neither nitric oxide (NO) synthase inhibitor nor NO scavenger. The quantal transmitter release was not potentiated by NO donors, e.g., sodium nitroprusside. The NE-induced potentiation and its enhancement by IBMX was antagonized by two inhibitors of protein kinase G (PKG), Rp isomer of 8-(4-chlorophenylthio) guanosine-3', 5'-cyclic monophosphorothioate and KT5823. As with NE-induced potentiation, the effects of 8Br-cGMP on both the resting intraterminal [Ca2+] ([Ca2+]i) and the action potential-dependent increment of [Ca2+]i (DeltaCa) in the presynaptic terminal were negligible. The reduction of the paired pulse ratio of EPSC is consistent with the notion that the NE- and cGMP-dependent potentiation of transmitter release was attributable mainly to an increase of the exocytotic fusion probability. These results indicate that NE binds to a novel adrenergic receptor that activates guanylyl cyclase and that accumulation of cGMP activates PKG, which may phosphorylate a target protein involved in the exocytosis of synaptic vesicles.

Adrenergic Antagonists↗

PubMed1993

Potentiation of nerve growth factor-induced alterations in cholinergic fibre length and presynaptic terminal size in cortex of lesioned rats by the monosialoganglioside GM1.

The effect of monosialoganglioside GM1 and/or nerve growth factor treatment on the cholinergic innervation of the rat cortex was studied using both light- and electron-microscopic techniques assisted by image analysis. Adult male Wistar rats were unilaterally decorticated and received continuous infusions, via minipump, of vehicle, GM1 (1.5 mg/day) and/or nerve growth factor (12 micrograms/day) into the cerebroventricular space. Treatments were initiated immediately post-lesion and ended after seven days. Thirty days post-lesion (i.e. 23 days after the end of drug administration) brains were processed for choline acetyltransferase immunocytochemistry for either light- or electron-microscopic analysis. At this time-point choline acetyltransferase-immunoreactive neurons in the ipsilateral nucleus basalis magnocellularis were significantly reduced in size especially in the mid portion of this nucleus, in lesion vehicle-treated rats. Moreover, decreases in choline acetyltransferase immunoreactive fibre length (ranging from 31 to 50%) and varicosity number (ranging from 26 to 39%) occurred in all cortical layers within a portion of the remaining cortex of these animals. Monosialoganglioside GM1 or nerve growth factor treatment equally attenuated deficits in nucleus basalis magnocellularis cell size and cortical choline acetyltransferase immunoreactive fibre length. However, nerve growth factor, but not monosialoganglioside GM1 treatment also increased choline acetyltransferase-immunoreactive varicosity number above control levels. In lesioned rats which received both nerve growth factor and the monosialoganglioside GM1, the mean cross-sectional area of nucleus basalis magnocellularis cholinergic neurons did not differ significantly from control values. By contrast, cortical choline acetyltransferase-immunoreactive fibre length and varicosity number were significantly increased above control values and that induced by nerve growth factor treatment alone. Quantitative electron-microscopic analysis showed that cholinergic boutons in cortical layer V were considerably shrunken in lesioned vehicle-treated rats and that GM1 treatment failed to significantly attenuate this deficit. However, exogenous nerve growth factor provoked a significant increase (35% above control values) in cortical cholinergic presynaptic terminal size which was even further augmented by concurrent GM1 treatment (69% above control values). This trophic factor-induced increase in bouton size was confirmed using serial electron microscopy and computer-assisted three-dimensional reconstruction of the cholinergic varicosities. The number of synaptic contacts in cortical layer V was also found to be significantly reduced (45% of control values) in lesioned vehicle-treated rats but was maintained at control levels by exogenous GM1 treatment. In addition, a significant increase (95% above control levels) in the number of choline acetyltransferase-immunoreactive boutons with synaptic differentiations was noted in lesioned nerve growth factor-treated rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

The cytoskeletal architecture of the presynaptic terminal and molecular structure of synapsin 1.

We have examined the cytoskeletal architecture and its relationship with synaptic vesicles in synapses by quick-freeze deep-etch electron microscopy (QF.DE). The main cytoskeletal elements in the presynaptic terminals (neuromuscular junction, electric organ, and cerebellar cortex) were actin filaments and microtubules. The actin filaments formed a network and frequently were associated closely with the presynaptic plasma membranes and active zones. Short, linking strands approximately 30 nm long were found between actin and synaptic vesicles, between microtubules and synaptic vesicles. Fine strands (30-60 nm) were also found between synaptic vesicles. Frequently spherical structures existed in the middle of the strands between synaptic vesicles. Another kind of strand (approximately 100 nm long, thinner than the actin filaments) between synaptic vesicles and plasma membranes was also observed. We have examined the molecular structure of synapsin 1 and its relationship with actin filaments, microtubules, and synaptic vesicles in vitro using the low angle rotary shadowing technique and QF.DE. The synapsin 1, approximately 47 nm long, was composed of a head (approximately 14 nm diam) and a tail (approximately 33 nm long), having a tadpole-like appearance. The high resolution provided by QF.DE revealed that a single synapsin 1 cross-linked actin filaments and linked actin filaments with synaptic vesicles, forming approximately 30-nm short strands. The head was on the actin and the tail was attached to the synaptic vesicle or actin filament. Microtubules were also cross-linked by a single synapsin 1, which also connected a microtubule to synaptic vesicles, forming approximately 30 nm strands. The spherical head was on the microtubules and the tail was attached to the synaptic vesicles or to microtubules. Synaptic vesicles incubated with synapsin 1 were linked with each other via fine short fibrils and frequently we identified spherical structures from which two or three fibril radiated and cross-linked synaptic vesicles. We have examined the localization of synapsin 1 using ultracryomicrotomy and colloidal gold-immunocytochemistry of anti-synapsin 1 IgG. Synapsin 1 was exclusively localized in the regions occupied by synaptic vesicles. Statistical analyses indicated that synapsin 1 is located mostly at least approximately 30 nm away from the presynaptic membrane. These data derived via three different approaches suggest that synapsin 1 could be a main element of short linkages between actin filaments and synaptic vesicles, and between microtubules and synaptic vesicles, and between synaptic vesicles in the nerve terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗

PubMed1983

Immunocytochemical evidence for tubulin in the presynaptic terminal of synaptosomes.

Ultrastructural studies of intact tissue rarely show presynaptic microtubules, and immunocytochemical studies on tissue sections have previously been unable to demonstrate tubulin in the nerve terminal. In contrast, a microtubular coil can be readily detected in the presynaptic nerve terminal of synaptosomes. We have developed an immunocytochemical procedure on the synaptosome preparation and demonstrated, using monoclonal antibodies, that in the presynaptic terminal alpha and beta tubulin subunits are specifically restricted to the equatorial microtubular coil.

Animals↗

PubMed1990

Quantitative immunohistochemistry of synaptophysin in human neocortex: an alternative method to estimate density of presynaptic terminals in paraffin sections.

Currently available specific synaptic markers have made it possible to estimate the synaptic density by immunochemical techniques. In the present study we labeled the neocortical presynaptic terminals in histological sections of human autopsy tissue with a monoclonal antibody against synaptophysin. The characteristic granular neuropil reaction was quantified by measuring the average optical density (OD) in the different layers of the parietal cortex with the aid of image analysis equipment. The raw neuropil OD was corrected by subtracting the OD of the white matter in the same section. Our study showed that consistent microdensitometric results can be obtained on 5-microns paraffin sections from specimens with less than 8 hr of post-mortem time before fixation, incubated with 5 micrograms/ml of anti-synaptophysin. The corrected OD measurements were slightly larger in neocortical layers II, III, and V than in layers I, IV, and VI, but the differences were not statistically significant. In area 17, layer IV was denser than the others. We conclude that with certain precautions this method can be used to measure relative amounts of synaptophysin-like immunoreactivity and to infer the density of presynaptic boutons in human situations and in animal models.

Aged↗

PubMed1986

Increased Ca-uptake of presynaptic terminals during long-term potentiation in hippocampal slices.

A combined electrophysiological and neurochemical study was performed on the CA1 area of hippocampal slices in an attempt to identify changes in presynaptic nerve terminal function in long-term potentiation (LTP). After controlled induction of LTP in CA1, the activated region was subjected to subcellular fractionation followed by 45Ca2+ uptake determinations. Synaptosomes prepared from slices in which LTP has been induced showed a faster risetime and a higher level of saturation for K+-induced Ca-uptake than those derived from unstimulated and stimulated control slices. These findings point to a participation of presynaptic terminals in long-term potentiation.

Animals↗

PubMed1999

Two components of transmitter release from the chick ciliary presynaptic terminal and their regulation by protein kinase C.

1. A study was made of the effects of phorbol ester (phorbol 12-myristate 13-acetate, PMA, 0.1 microM) on the two components of evoked transmitter release, namely the fast synchronous and the slow asynchronous components, from the giant presynaptic terminal of the chick ciliary ganglion. The excitatory postsynaptic currents (EPSCs) were recorded under whole-cell voltage clamp of the postsynaptic neuron. 2. The decay time constant of the slow component was prolonged by replacing Ca2+ with Sr2+. In 5 mM [Sr2+]o the fast component decayed with a time constant of 2.6 +/- 1.4 ms whereas the slow component decayed with a time constant of 19 +/- 7 ms. 3. When stimulated with twin pulses with a short interpulse interval, the fast component of the second EPSC was often depressed whereas the slow component was usually facilitated. Both components were positively dependent on [Sr2+]o in a saturable manner, but the fast component approached its maximum at a lower [Sr2+]o than the slow component. 4. PMA potentiated both the fast and slow components to a similar extent and with a similar time course. For each component, the effect of PMA was less potent at high [Sr2+]o than at low [Sr2+]o. For either the fast or the slow component the PMA-induced potentiation was accompanied by a reduction in the paired-pulse ratio (PPR). 5. Despite the different dissociation constant for dextran-conjugated fura-2, the fluorescent ratio for intraterminal [Sr2+] ([Sr2+]i) decayed to the baseline after the nerve-evoked increment with a time course similar to that for [Ca2+]i, suggesting that intraterminal Sr2+ is buffered less efficiently than Ca2+. PMA did not increase the [Sr2+]i transients produced by stimulation of the presynaptic oculomotor nerve. 6. It is suggested that protein kinase C (PKC) modulates both the fast and slow components through common molecular mechanisms that upregulate the Sr2+ sensitivity of the vesicle fusion probability.

Algorithms↗