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J Vautrin

Publications and source records attributed to J Vautrin.

At least 19 recordsLinked to original sources
PubMed2001

Contribution of the plasmalemma to Ca2+ homeostasis in hair cells.

Calcium influx through transduction channels and efflux via plasmalemmal Ca(2+)-ATPases (PMCAs) are known to contribute to calcium homeostasis and modulate sensory transduction in vertebrate hair cells. To examine the relative contributions of apical and basolateral pathways, we analyzed the calcium dynamics in solitary ciliated and deciliated guinea pig type I and type II vestibular hair cells. Whole-cell patch-clamp recordings demonstrated that these cells had resting potentials near -70 mV and could be depolarized by 10-20 mV by superfusion with high potassium. Fura-2 measurements indicated that ciliated type II cells and deciliated cells of either type had low basal [Ca(2+)](i), near approximately 90 nm, and superfusion with high potassium led to transient calcium increases that were diminished in the presence of Ca(2+) channel blockers. In contrast, measurements of type I ciliated cells, hair cells with large calyceal afferents, were associated with a higher basal [Ca(2+)](i) of approximately 170 nm. High-potassium superfusion of these cells induced a paradoxical decrease in [Ca(2+)](i) that was augmented in the presence of Ca(2+) channel blockers. Optical localization of dihydropyridine binding to the kinocilium suggests that they contain L-type calcium channels, and as a result apical calcium influx includes a contribution from voltage-dependent ion channels in addition to entry via transduction channels localized to the stereocilia. Eosin block of PMCA significantly altered both [Ca(2+)](i) baseline and transient responses only in ciliated cells suggesting that, in agreement with immunohistochemical studies, PMCA is primarily localized to the bundles.

Animals↗
PubMed2000

Surface-accessible GABA supports tonic and quantal synaptic transmission.

Exocytosis is commonly viewed as the only secretory process able to account for quantal forms of fast synaptic transmission. However, the demonstrated variability and composite properties of miniature postsynaptic signals are not easily explained by all-or-none exocytotic discharge of transmitter in solution from inside vesicles. Recent studies of endocrine secretion have shown that hormone release does not coincide with exocytosis due to its trapping in the core matrix of the granule. Thus, we tested whether the synaptic transmitter GABA could also be held in a matrix before being released. Using confocal microscopy and flow cytometry of embryonic rat hippocampal neurons, we found a GABA immunoreaction at the surface of live cell bodies and growth cones that coincided spatially and quantitatively with the binding of tetanus toxin fragment C (TTFC). TTFC binds predominantly at membrane sites containing the trisialoglycosphingolipid GT1b. Using flow cytometry, GT1b-containing liposomes preincubated in 100 nM GABA exhibited the same relationship between GABA and TTFC surface binding as found on neurons and growth cones. Embryonic neurons differentiated in culture expressed initially a tonic, and after 3-5 days, transient, postsynaptic signals mediated by GABA acting at GABA(A) receptor/Cl(-) channels. A stream of saline applied to the neuronal surface rapidly and reversibly suppressed both tonic and transient signals. A brief application of the GABAmimetic isoguvacine immediately transformed both tonic and transient GABAergic signals into tonic and transient isoguvacinergic signals. These results and those in the literature are consistent with an immediately releasable compartment of transmitter accessible from the presynaptic surface.

Adsorption↗
PubMed1999

Miniature EPSPs and sensory encoding in the primary afferents of the vestibular lagena of the toadfish, Opsanus tau.

The synaptic activity transmitted from vestibular hair cells of the lagena to primary afferent neurons was recorded in vitro using sharp, intracellular microelectrodes. At rest, the activity was composed of miniature excitatory postsynaptic potentials (mEPSPs) at frequencies from 5 to 20/s and action potentials (APs) at frequencies betwen 0 and 10/s. mEPSPs recorded from a single fiber displayed a large variability. For mEPSPs not triggering APs, amplitudes exhibited an average coefficient of variance (CV) of 0.323 and rise times an average CV of 0.516. APs were only triggered by mEPSPs with larger amplitudes (estimated 4-6 mV) and/or steeper maximum rate of rise (10.9 mV/ms, +/- 3.7 SD, n=4 experiments) compared to (3.50 mV/ms, +/-0.07 SD, n=6 experiments) for nontriggering mEPSPs. The smallest mEPSPs showed a fast rise time (0.99 ms between 10% and 90% of peak amplitude) and limited variability across fibers (CV:0.18) confirming that they were not attenuated signals, but rather represented single-transmitter discharges (TDs). The mEPSP amplitude and rise-time relationship suggests that many mEPSPs represented several, rather than a single pulse of secretion of TDs. According to the estimated overall TD frequency, the coincidence of TDs contributing to the same mEPSP were not statistically independent, indicating a positive interaction between TDs that is reminiscent of the way subminiature signals group to form miniature signals at the neuromuscular junction. Depending on the duration and intensity of efferent stimulation, a complete block of AP initiation occurred either immediately or after a delay of a few seconds. Efferent stimulation did not significantly change AP threshold level, but abruptly decreased mEPSP frequency to a near-complete block that followed the block of APs. Maximum mEPSP rate of rise decreased during, and recovered progressively after, efferent stimulation. After termination of efferent stimulation, mEPSP amplitude did not recover instantly and for a few seconds the amplitude distribution of synaptic events showed fewer large-amplitude events than during the control period. This confirms that mEPSP amplitude and rate of rise properties, which are critical for triggering afferent APs, are modified by efferent activity. The depression of afferent AP firing during efferent stimulation corresponded to a decrease in mEPSP frequency and, to a lesser extent, a decrease in mEPSP amplitude and rate of rise, suggesting, a decrease in the level of interaction among TDs contibuting to a mEPSP.

Action Potentials↗
PubMed1999

K+-dependence of Na+-Ca2+ exchange in type I vestibular sensory cells of guinea-pig.

The properties of the vestibular Na+-Ca2+ exchanger in mammalian type I vestibular sensory cells were studied using fura-2 fluorescence and immunocytochemical techniques. In the absence of external Na+, the activation of Na+-Ca2+ exchange in reverse mode required the presence of external K+ (K+o) and depended on K+o concentration. Alkali cations Rb+ and NH4+ but not Li+ or Cs+ substituted for K+o to activate the exchange. For pressure applications of 10 mm K+, the contribution of voltage-sensitive calcium channels to the increase in [Ca2+]i was < 15%. The dependence of the exchange on [K+]o was also recorded when the membrane potential was clamped using carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP) and monensin ionophores. In these conditions, where there was no intracellular Na+, the increase in [Ca2+]i was completely blocked. These physiological results suggest that in reverse mode, Ca2+ entry is driven by both an outward transport of Na+ and an inward transport of K+. The dependence of the vestibular Na+-Ca2+ exchanger on K+ is more reminiscent of the properties of the retinal type Na+-Ca2+ exchanger than those of the more widely distributed cardiac type exchanger. Moreover, the immunocytochemical localization of both types of exchange proteins in the vestibular sensory epithelium confirmed the presence in the vestibular sensory cells of a Na+-Ca2+ exchanger which is recognized by an antibody raised against retinal type and not by an antibody raised against the cardiac type.

Alkalies↗
PubMed1997

GABA induces GABAergic MSCs in cultured embryonic rat thalamic neurons.

Application of 0.1-10 microM GABA in the vicinity of cultured embryonic rat thalamic neurons recorded with patch pipettes in the presence of 2 microM TTX induced or increased the frequency of miniature synaptic currents (MSCs) that reversed polarity at the Cl- equilibrium potential. These MSCs were blocked by the GABAA receptor antagonist bicuculline and exhibited exponential decay kinetics that closely paralleled those estimated from fluctuation analysis of Cl- channels activated pharmacologically by applying 1-10 microM GABA to the same cells. We conclude that the MSCs are mediated by GABA. Application of the GABAA receptor agonist muscimol activated Cl- current but failed to induce GABAergic MSCs while submicromolar concentrations of GABA evoked GABAergic MSCs but did not activate Cl- channels. The GABAB receptor agonist (-)baclofen did not mimic GABA in inducing MSCs. Induction of GABAergic MSCs by GABA required extracellular Ca2+. Verapamil and Co2+, which block voltage-dependent calcium channels, completely blocked GABA-induced MSCs independent of their effects on the direct activation of a Cl- current response. The results indicate that GABA can trigger GABAergic Cl(-)-dependent MSCs in a Cao(2+)-dependent manner. The mechanism may involve a novel receptor and/or signal transduction pathway.

Animals↗
PubMed1996

Hypertonic treatment reversibly increases the ratio of giant skew-miniature endplate potentials to bell-miniature endplate potentials.

Miniature endplate potentials were recorded from single frog muscle fibers before, during and after treatment with hypertonic saline (200-500 mM NaCl or Na gluconate added to frog saline). Miniature endplate potential amplitude distributions were plotted from small muscle fibers so that the modes and ratios of the skew-miniature endplate potential to bell-miniature endplate potential classes could be defined. Muscle fibers were voltage clamped with two electrodes to determine the input resistance before, during and after treatment. Input resistance increased from two to 100 times during treatment and rapidly fell towards control values (no more than 30% greater) when preparations were returned to normal frog saline. Short duration treatments with 200-300 mM hypertonic salines immediately increased frequencies (100-fold) of both skew-miniature endplate potential and bell-miniature endplate potential classes. Preparations when returned to normal frog saline after a few minutes of treatment showed control miniature endplate potential distributions within minutes. One to two hour treatments left only the skew-miniature endplate potential class and with hour-long recovery periods bell-miniature endplate potentials reappeared and ratios of skew-miniature endplate potential to bell-miniature endplate potential classes returned to control values. Treatment with 500 mM NaCl added to frog saline immediately increased the percentage of skew-miniature endplate potentials (from 2 to 50%) with little or no increase in overall miniature endplate potential frequencies. The mode of the skew-miniature endplate potential class was unchanged after hypertonic treatment, whereas that of the bell-miniature end plate potential class either remained about the same size or decreased depending on the duration of treatment. The number and percentage of giant-miniature endplate potentials belonging to the skew-miniature endplate potential class increased as a function of the duration of 200-300 mM hypertonic saline treatments. Most giant-miniature endplate potentials had a slow rising phase with a foot and/or breaks demonstrating a composite structure. Sequentially recorded giant-miniature endplate potentials had similar initial slopes indicating either repetitive releases from single sites or releases from cooperative sites. After hypertonic treatment the bell-miniature endplate potential size was never more than that expected with the increase (under 30%) in input resistance. The results presented here are completely different from those of Yu and Van der Kloot [(1991) J. Physiol. 433, 677-704] who reported that the bell-miniature endplate potential amplitude was increased two- to four-fold after hypertonic treatment. The wide range of results in the ratio of skew-miniature endplate potential to bell-miniature endplate potential classes is discussed in regards to the quantal hypothesis which is based on a single class of immutable amounts of transmitter; and, a hypothesis based on a dynamical process that meters transmitter in subunit amounts to control miniature endplate potential size and class during release.

Animals↗
PubMed1995

How can exocytosis account for the actual properties of miniature synaptic signals?

It is broadly accepted that a postsynaptic "miniature" is the most elementary chemically transmitted signal and results from the all-or-none release of transmitter packaged in a single presynaptic vesicle. Hitherto, it has not been possible to directly verify this renowned representation, although it is consistent with evidence of vesicle traffic and, following an intense period of release, vesicle depletion. However, vesicle traffic involving molecular components similar to those implicated in transmitter release has been attributed to other functions including membrane repair. Furthermore, as a number of investigators have recently proposed, miniature signals recorded at peripheral and central synapses may actually reflect several rather than a single discharge of transmitter. It is not clear whether such putative multiple-discharge miniatures represent near-synchronous exocytoses of several vesicles or a burst of openings in a pore that couples a vesicle with the outer membrane. In any case, despite the popularity of the vesicular hypothesis, the molecular mechanism involved in synchronizing fast elementary secretion has not yet been elucidated. Interdependencies among subminiature discharges composing a miniature have suggested that the underlying process is a regenerative signal restricted to a presynaptic terminal unit, confirming Fatt and Katz's first speculation on miniatures, which was not vesicular exocytosis [Fatt and Katz (1952), J. Physiol., 117:109-128]. Here we discuss the possibility that this regenerative signal might be a localized cytosolic Ca2+ transient and attempt to reconcile this hypothesis with the exocytotic models proposed to explain fast transmitter release.

Animals↗
PubMed1995

Exogenous GABA persistently opens Cl- channels in cultured embryonic rat thalamic neurons.

We recorded whole-cell Cl- currents in cultured embryonic rat thalamic neurons by brief applications of GABA or the structural analogue muscimol. In 17 of 141 neurons (12%) the Cl- current persisted for a minute or more after the pipette was removed from the bath. Cl- current never persisted after muscimol exposure even in those cells exhibiting persistent GABA-activated currents (PGC). The half decay times (T50) of PGCs were exponentially and asymptotically related to the duration of GABA exposure and could be interrupted or completely aborted by low-pressure application of saline. PGCs were insensitive to membrane potential, to Tiagabine, a nipecotic acid analogue known to block GABA uptake, and persisted in Cao(2+)-free medium. Fluctuation analysis revealed that PGCs exhibited inferred Cl- channel properties whose kinetic components and estimated average elementary conductance showed no significant difference from those estimated during GABA exposure. The relative contribution of low frequency components was consistently reduced and that of high frequency components modestly increased during PGC compared to those recorded during GABA exposure. Taken together, the results suggest the existence of a superficial compartment in these embryonic neurons that can momentarily accumulate and release exogenous GABA.

Animals↗
PubMed1994

Fast presynaptic GABAA receptor-mediated Cl- conductance in cultured rat hippocampal neurones.

1. Hippocampal neurones cultured from the 18-day-old embryonic rat for 3 days to 3 weeks were recorded with Cl(-)-filled patch pipettes. Spontaneous synaptic currents, which reversed at the equilibrium potential for Cl- ions (ECl) and were blocked by the GABAA (gamma-aminobutyric acid) receptor antagonists bicuculline or picrotoxin, were recorded in every culture. At 25 degrees C and -80 mV they decayed with a time constant > or = 20 ms that invariably increased at positive potentials. After 2 weeks, 50-75% of all neurones were GABA immunoreactive. 2. In pairs-recordings, coincident synaptic currents in both cells were either spontaneous or evoked by stimulation of one cell. In the presence of tetrodotoxin and using pipettes containing lidocaine (lignocaine) N-ethyl bromide, coincident spontaneous Cl- transients still occurred in both neurones far more frequently than expected by chance. 3. Holding the potential of one neurone at a positive value reversed the synaptic transients in that cell and, in half of the cells, increased the frequency of coincident events in both cells. 4. In neurones where depolarization increased the frequency of coinciding events and all regenerative current apparent at the soma was abolished, short depolarizing pulses occasionally evoked all-or-none, pre- and postsynaptic currents with matching transmission failures and identical delays in transmission. 5. The results suggest that the same pulse of GABA simultaneously activates GABAA receptor-coupled Cl- channels on both sides of the same synaptic cleft, producing immediate auto-transmission in the absence of collaterals or interneurones.

Animals↗
PubMed1993

Tonic GABA secretion of cultured rat hippocampal neurons rapidly transformed by Zn2+ into quantal release.

Different mechanisms of neurotransmitter secretion at synapses have been ascribed to quantal, transient signals [4-9] and to continuous, tonic activity [11, 21, 25]. Quantal transmission is imputed to be the release of transmitter packets, or quanta [6], assembled and stored in vesicles present in presynaptic terminals [2,8]. We report that 300 microM Zn2+ rapidly transformed tonic Cl- conductance mediated by the transmitter gamma-aminobutyric acid (GABA) into transient synaptic-like signals. After addition of Zn2+, the size of the elementary fluctuations in the Cl- current progressively increased while randomly activated Cl- channel kinetics remained unchanged and accounted for the bi-exponential time course of average transient decay. The results suggest that Zn2+ rapidly transforms tonic GABA secretion into quantal-like transient release.

Animals↗
PubMed1993

Quantal and subquantal GABAergic transmissions in cultured rat hippocampal neurons.

At the neuromuscular junction, spontaneous miniature excitatory synaptic currents mediated by acetylcholine are considered elementary, "quantal" transmissions. These miniature conductances can be quantitatively dichotomized into a large-mode class whose mode is the mean of a normal, bell-shaped distribution and a small-mode class whose distribution is skewed to lower values with its mode being a fraction of the large-mode class. The large-mode class constitutes the population of synaptic signals originally utilized to formulate tenets of "quantal" transmission, which have been tacitly adopted in more recent studies of fast transmission at central synapses. Large- and small-mode conductance classes of inhibitory synaptic elementary conductances mediated by GABA have now been recorded in cultured hippocampal neurons (Vautrin J, Schaffner AE, Barker JL, 1991, Neurosci Lett 138:67). Pairs of hippocampal neurons were patch-recorded at optimal signal-to-noise and, using time course analysis, two elementary fluctuations (0.1-0.3 nS and 1-2 nS) were found within synaptic conductances evoked either by presynaptic action potentials or by presynaptic terminal stimulation. These results were interpreted with a simple model that shows how different frequencies of unitary GABA release can generate either small-mode, skew-distributed conductance (0.5-3 kHz) or large-mode, normally-distributed conductances (> or = 10 kHz). Only the latter satisfies the original tenets of the classic quantal theory.

Action Potentials↗
PubMed1993

Frequency modulation of transmitter release.

In 1952 Fatt and Katz recorded at a frog neuromuscular junction while stimulating the nerve and found "... that successive endplate potential responses varied in a step-like manner, corresponding to units of miniature endplate potentials" (J Physiol 117, 109-128). This led them to propose that fast neuromuscular transmission is 'quantal'. Quantal release is now commonly ascribed to a vesicular form of neurosecretion since vesicles have routinely been visualized in presynaptic terminals. The vesicular hypothesis (Del Castillo and Katz, 1955) assumes that quanta, or 'transmitter packets of standard size', are assembled and stored in the numerous vesicles routinely identified in micrographs of virtually all central and peripheral presynaptic nerve terminals. Simply stated, this model predicts that each one of the miniature synaptic signals (MSSs) follows from the exocytosis of one vesicle's contents. However, the time required for membrane fusion preceding exocytosis (Almers and Tse, 1990) and the variability in MSS amplitude and time course (Vautrin et al, 1992a,b) cannot readily be reconciled by a simple, exocytotic model of quantal release from preloaded vesicles. These difficulties with the original model have led us to re-evaluate MSSs generated at the classical peripheral synapse, the cholinergic neuromuscular junction of the mouse diaphragm, as well as at central synapses between embryonic hippocampal neurons mediated by gamma-aminobutyric acid (GABA). At these synapses, the release of GABA is also assumed to have classical quantal properties like peripheral acetylcholine release (Edwards et al, 1990). Our results show that at both synapses, progressive alterations in elementary signal properties can be induced in a remarkably rapid manner. The original report of preferred amplitudes and intervals in the spontaneous miniature signals (Fatt and Katz, 1952) has repeatedly been confirmed and is here incorporated into a dynamic model of fast synaptic transmission. Although MSSs exhibit variable rise-times and peak amplitudes, they can both be described in terms of synchronization of transmitter release. We have reviewed many experimental findings, which together strongly suggest that the original interpretation of Fatt and Katz (1952) regarding MSSs as reflecting the non-propagated 'neurogenic' activity of 'terminal spots' may be a useful concept to pursue since it may help to explain part of the underlying molecular basis of quantal release.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

High percentage of skew-distributed miniature endplate currents in old mice.

Muscle fibers from diaphragms of old (14 to 24 months) and young adult (1 to 2 months) inbred (strain C57BL/6) mice were voltage clamped at -140 mV with two microelectrodes near the neuromuscular junction. Miniature endplate currents (MEPCs) were digitized so that peak amplitudes and rise times could be determined. MEPC amplitude distributions from old mice varied greatly between fibers from the same diaphragm, and the mean MEPC amplitude (2.1 +/- 0.83 nA, mean +/- SD) was smaller than in young mice (5.2 +/- 0.59 nA). In old mice, some (50%) amplitude distributions were bell shaped, composed of mainly bell-MEPCs with a 2- to 5-nA mode, whereas others (30%) were skewed with a 0.5- to 2-nA mode, and some (20%) showed two peaks, representing both skew- and bell-MEPC classes. MEPC rise-time distributions from old mice varied between fibers, although they all had similar modes. Some (30%) were bell shaped (similar to those in young mice) with a mode between 0.5 and 1 ms (coefficient of variation, 40%), but most distributions were skewed. Endplates with smaller mean MEPC amplitudes showed a longer mean rise time, and for a given junction, MEPC amplitudes were correlated positively to the corresponding rise times. This observation, together with analyses of the rising phases, indicates that MEPCs with long rise times were not generated at remote sites. We discuss our results with regard to the hypothesis of a dynamic formation of transmitter packets, and we attribute long rise time, skew-MEPCs to a prolonged release process. During aging, the state of release that generates the skew-MEPC class appears more dominant than the state generating the bell-MEPC class.

Aging↗
PubMed1992

Two classes of spontaneous GABA-mediated miniature synaptic currents in cultured rat hippocampal neurons.

Amplitude and time course of spontaneous gamma-aminobutyric acid (GABA)-mediated miniature postsynaptic currents (MPSCs), recorded in cultured embryonic hippocampal neurons in presence of either tetrodotoxin (TTX) or increased external [Mg2+/Ca2+] ratio, revealed that they form two classes. The distribution of the most commonly recorded MPSCs was skewed both in terms of peak amplitude and rise-time (skew-MPSCs, mode: 70-120 pS). Another, less frequent class (mode: 1-3 nS) formed bell-shaped (bell-MPSCs) amplitude and rise-time distributions. MPSC initial slope did not correlate with rise time, indicating that smaller MPSCs were not electrotonically attenuated. Bell-MPSCs did not result from the integration of skew-MPSCs and both classes appeared to be composed of subunits.

Animals↗
PubMed1992

Miniature endplate potentials induced by ammonium chloride, hypertonic shock, and botulinum toxin.

Intracellular recordings were made at the neuromuscular junction (NMJ) of the mouse diaphragm to study alteration of miniature endplate potential (MEPP) amplitude and rise time after different treatments. Following either hyperosmotic shock or 3 to 5 min of incubation in 10 to 50 mM ammonium chloride (NH4Cl) (replacing NaCl, a treatment which is known to raise intracellular pH) MEPP frequencies increased and the amplitudes of MEPPs decreased. These treatments as well as type A botulinum toxin (BoTx) gradually prolonged the rising phase of some MEPPs, which increased their time-to-peak (slow-MEPPs; Vautrin and Kriebel: Neuroscience 41:71-88, 1991) and increased eventually their amplitude. Fasciculation after hyperosmotic shock or during NH4Cl challenge was blocked by D-tubocurarine and was due to large slow-MEPPs that reached threshold for the muscle fiber action potential. The development of fasciculation provided the time course for the development of giant-MEPPs. Increased frequency of giant MEPP is accompanied by a block of the nerve-evoked muscle contraction. Effects of BoTx on spontaneous release were functionally antagonized either by NH4Cl or hyperosmotic shock. NH4Cl delayed BoTx blockage of bell-MEPPs. Data suggest that BoTx alters the formation of transmitter packets gradually but similarly to other treatments which increase incidence of skew-MEPPs.

Action Potentials↗
PubMed1992

Focal, extracellular recording of slow miniature junctional potentials at the mouse neuromuscular junction.

Miniature endplate potentials (MEPPs) with slow rising phase can be attributed either to burst of transmitter releases or to distortion of conduction from remote releasing sites. The spontaneous activity of neuromuscular junctions recorded extracellularly at mouse diaphragms using sharp electrodes was analyzed to test these two hypotheses. The miniature junctional potentials (MEJPs) frequencies observed intracellularly as compared to MEPP frequency measured intracellularly in controls indicate that most events recorded extracellularly are induced by the presence of the electrode. All types of MEPPs (bell-MEPPs, skew-MEPPs, slow-, and giant MEPPs) previously described with intracellular recording methods (Vautrin and Kriebel, Neuroscience 41:71-88, 1991) were observed extracellularly and showed similar characteristics. This means that the presynaptic and postsynaptic zones that generate these synaptic events are restricted within areas of a few micrometers squared of synaptic contact. Long rise times of extracellularly recorded synaptic spontaneous events may be explained by multiple transmitter releases at intervals shorter than the rise time of individual events, which postsynaptic responses fuse into a single peak.

Animals↗
PubMed1992

Further evidence for the dynamic formation of transmitter quanta at the neuromuscular junction.

Fatt and Katz (Nature 166:597-598, 1950; J Physiol 117:109-128, 1952) attributed miniature endplate potentials (MEPPs) to the action of a standard quantity of transmitter, the quantum (Del Castillo and Katz, J Physiol 124:560-573, 1954). Quantal packets of transmitter were proposed to be preformed (Del Castillo and Katz, In CNRS Paris (Ed): "Microphysiologie comparée des éléments excitables" 67:245-258, 1957) and stored in large numbers in the motor nerve terminal. Statistical analyses of intervals between MEPPs and numbers of quanta composing small endplate potentials indicated that quantal release was a random process and that release sites functioned independently of each other. With the discovery of synaptic vesicles it was proposed that each contained one quantum of transmitter. The quantal-vesicular hypothesis (Del Castillo and Katz, as cited above) fails, however, to explain amplitude distributions of MEPPs that are skewed and/or that show multiple peaks (Kriebel et al., Brain Res Review 15:167-178, 1990). The drop formation process (Shaw, "The Dripping Faucet as a Model Chaotic System," Santa Cruz, CA: Aerial Press, Inc., 1984) was shown to generate amplitude classes of drops that were similar to classes of MEPPs which suggested that rapid changes in quantal size and ratios of skew- to bell-MEPPs could be explained with a simple dynamic process which determines quantal size at the moment of release (Kriebel et al., as cited above, 1990). Further similarities between miniature endplate currents (MEPCs) and the formation of drops are reported here. We found that rapid changes in MEPC amplitudes and time courses, which accompany an increase in frequency, mimic changes in drop sizes that accompany increases in flow rate. MEPC intervals have a minimum and their distributions are comparable to those of drop intervals. During an increased rate of transmitter release, MEPP amplitudes and intervals were positively correlated. The results suggest that spontaneously released transmitter "packets" are formed at the moment of release and that transmitter supply to the process that forms packets is continuous.

Animals↗