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M K Worden

Publications and source records attributed to M K Worden.

12 recordsLinked to original sources
PubMed1999

Evaluation of quantal neurosecretion from evoked and miniature postsynaptic responses by deconvolution method.

A new deconvolution algorithm has been developed for evaluation of quantal content and its variability at high-output synapses. The algorithm derives the distribution of the number of neurosecretory quanta released in a trial (M) from the measured sizes of evoked postsynaptic responses. The deconvolution employs the distribution of quantal sizes obtained by measuring sizes of miniature postsynaptic responses. The distribution of quantal content M is derived by ridge regression method from the distributions of sizes of the responses and of quantal sizes. The deconvolution method was applied to postsynaptic responses from the excitory innervation of lobster dactyl opener muscle obtained by focal extracellular recordings. The obtained solution (distribution of M) had six to eight components and was stable. The method was tested by the analysis of simulated multiquantal responses. For the simulated responses, the ridge regression solution reproduced the imposed distribution of M within the limits of the calculated confidence intervals. To further test the algorithm, the distribution of M at a low-output synapse was obtained both by deconvolution method and by the method of direct quantal counts. The results of these two methods were found to be in a very good agreement.

Action Potentials↗
PubMed1999

Asynchrony of quantal events in evoked multiquantal responses indicates presynaptic quantal interaction.

Asynchrony of quantal events in evoked multiquantal responses indicates presynaptic quantal interaction. We have analyzed the possibility of quantal interactions by inspecting action potential-evoked postsynaptic multiquantal responses recorded extracellularly from the lobster neuromuscular junction. These recorded responses were compared with simulated multiquantal responses constructed from statistically independent quantal events. The simulated multiquantal responses were generated by random superposition of single quantal responses aligned according to the timing of the action potential. The methods of analysis consisted of 1) the comparison of quantal contents obtained from direct counting or by measuring of the size of the responses and 2) the analysis of distributions of quantal latencies. This analysis revealed a large error in the detection of quantal events for responses simulated with no quantal interaction. In contrast, very few errors in quantal detection were made in the analysis of experimental recordings. Latency histograms of recorded responses demonstrate that the proportion of late quantal events (those with latencies of >/=5 ms) increased as a function of quantal content. This shift in latency histograms was not observed for simulated responses. Our interpretation is that quanta interact presynaptically to cause asynchrony of quantal events in evoked responses.

Action Potentials↗
PubMed1998

Modulation of vertebrate and invertebrate neuromuscular junctions.

Advances in our understanding of how the neuromuscular junction is modulated include an expanded appreciation of the many different types of modulatory influences, from soluble factors to second-messenger systems, to specific proteins in nerve and muscle. Recent studies indicate that modulation of neuromuscular function is effected on both the presynaptic and postsynaptic sides of the neuromuscular junction.

Animals↗
PubMed1997

Facilitation at the lobster neuromuscular junction: a stimulus-dependent mobilization model.

Frequency facilitation is a process whereby neurosecretion increases as a function of stimulation frequency during repetitive synaptic activity. To examine the physiological basis underlying facilitation, we have estimated the frequency dependence of the synaptic parameters n (number of units capable of responding to a nerve impulse) and P (average probability of responding) at the lobster neuromuscular junction. Both n and P increase as a function of frequency, suggesting that the efficiency of quantal docking and quantal fusion is regulated by repetitive synaptic activity. In experiments in which facilitation is strong and quantal content does not saturate over the frequency range tested, the value of P saturates at low frequencies of stimulation, and increases in quantal content at higher frequencies of stimulation are due to an increase in n. Therefore the value of P does not limit facilitation. We propose that transmitter release is limited by the rates of quantal mobilization and demobilization, and that each excitatory stimulus causes additional mobilization of quanta to dock at the presynaptic release sites. In such a model the binomial parameter n will correspond to the number of quanta docked at the release sites and available for release. We have developed and solved kinetic equations that describe how the number of docked quanta changes as a function of time and of stimulation frequency. The stimulus-dependent mobilization model of facilitation predicts that the reciprocal value of the quantal content depends linearly on the reciprocal product of the stimulation frequency and the probability of release. Fits of the experimental data confirm the accuracy of this prediction, showing that the model proposed here quantitatively describes frequency facilitation. The model predicts that high rates of quantal demobilization will produce strong frequency facilitation.

Algorithms↗
PubMed1996

An algorithm for high-resolution detection of postsynaptic quantal events in extracellular records.

A software package has been developed for the detection and measurement of extracellularly recorded postsynaptic quantal events evoked by neural stimulation. The algorithm is based on the identification of monotonic regions of a differentiated current signal and detects the small inflections and peaks of a postsynaptic response that result from the asynchronous presynaptic release of individual packets of neurotransmitter. Recorded and simulated postsynaptic responses have been used to verify the accuracy of the algorithm and to determine its resolution. The algorithm can accurately detect up to six individual quanta in a time period of 20 ms, with a resolution of 0.5-1.0 ms.

Action Potentials↗
PubMed1995

Peptide F1, an N-terminally extended analog of FMRFamide, enhances contractile activity in multiple target tissues in lobster.

The physiological actions of lobster peptide F1 (TNRNFLRFamide) have been examined on three different lobster nerve-muscle preparations (exoskeletal, cardiac and visceral). The peptide, which is found at high concentrations in a lobster neurosecretory gland, causes a long-lasting enhancement of contractility in each target tissue. On exoskeletal nerve-muscle preparations, peptide F1 has the following actions: (1) it potentiates transmitter release from nerve terminals innervating exoskeletal muscle, leading to an increase in both spontaneous and nerve-evoked release of transmitter; (2) it acts directly on the muscle, in the absence of nerve activity, to induce tonic contractions; and (3) it shows a potent desensitization that does not reverse with prolonged washing of the tissue. On each of the types of muscle examined, peptide F1 is active at nanomolar concentrations and is 3-4 orders of magnitude more potent than FMRFamide. These findings suggest that peptide F1 is a neurohormone with widespread myogenic actions throughout lobster peripheral tissues. The molecular mechanism(s) by which the peptide acts are not yet known, but do not appear to involve cyclic AMP or cyclic GMP.

Amino Acid Sequence↗
PubMed1994

A voltage-sensitive cation channel present in clusters in lobster skeletal muscle membrane.

The single channel properties of a voltage-sensitive cation channel are described in a study of ion channel activity in enzymatically induced blebs of lobster skeletal muscle membrane. This cation channel, one of several that are spontaneously active in excised patches from bleb membrane, can be distinguished from other channels on the basis of its large single channel conductance (293 pS), voltage-sensitive gating properties, the presence of a subconductance state of the fully open channel, and a weak selectivity for K > Na. At hyperpolarizing voltages, this channel displays flickering or bursting behavior, and a single state of the fully open channel is observed. At depolarizing voltages, the mean channel open time increases and a second longer-lived open state is observed. The voltage dependence of the mean channel open time and the linear i-V relation of this channel predict that the macroscopic current carried through this cation channel would be outwardly rectifying. Channels of this type are infrequently observed in this preparation, but when present in the patch are often present in multiple copies. We describe a statistical test for examining the clustering of ion channels in excised patches of membrane. The result of this test shows that the cation channels appear in clusters in the blebs.

Animals↗
PubMed1993

Ion channel activity in lobster skeletal muscle membrane.

Ion channel activity in the sarcolemmal membrane of muscle fibers is critical for regulating the excitability, and therefore the contractility, of muscle. To begin the characterization of the biophysical properties of the sarcolemmal membrane of lobster exoskeletal muscle fibers, recordings were made from excised patches of membrane from enzymatically induced muscle fiber blebs. Blebs formed as evaginations of the muscle sarcolemmal membrane and were sufficiently free of extracellular debris to allow the formation of gigaohm seals. Under simple experimental conditions using bi-ionic symmetrical recording solutions and maintained holding potentials, a variety of single channel types with conductances in the range 32-380 pS were detected. Two of these ion channel species are described in detail, both are cation channels selective for potassium. They can be distinguished from each other on the basis of their single-channel conductance and gating properties. The results suggest that current flows through a large number of ion channels that open spontaneously in bleb membranes in the absence of exogenous metabolites or hormones.

Animals↗
PubMed1988

Regeneration studies on a crayfish neuromuscular system. I. Connectivity changes after intersegmental nerve transplants.

The superficial flexor muscles of the crayfish are a neuromuscular system of a few muscle cells innervated by six neurons in a precise position-dependent pattern. The neurons are capable of regenerating their normal connectivity patterns within a short span of time when conditions are favorable. The superficial flexor muscles of the second and third segments, despite their similarities in neuronal and muscle cell size and number, have distinctive connectivity patterns; some homologous neurons form similar patterns but other homologous neurons form patterns that are reversed between segments. We transplanted each segment's nerve into each other's muscle in order to observe regeneration of the nerves into a target area that differed in connectivity patterns from their original muscle. During the first weeks of regeneration all neurons formed a connectivity pattern with more connections medially and declining connections laterally, a pattern determined by the medial location of the nerve transplant. This pattern is maintained for most of the neurons, but for some there is an eventual reduction in medial connections as maximum synapse formation shifts to the lateral muscle fibers. Three of the eight neurons studied were able to regenerate connectivity patterns that corresponded to their segment of origin and not to their host muscle. This suggests that intersegmental muscle differences are not influencing the formation of these connectivity patterns, so the neurons will follow their inherent synaptogenesis program.

Animals↗
PubMed1985

Model peptidergic systems at the insect neuromuscular junction.

The emergence of neuropeptides as a prominent neurotransmitter class raises fundamental new questions about modes of chemical signaling in the nervous system. These relate to the large number of peptides, their co-localization in neurons and to novel actions at innervated targets. Synaptic preparations in insects offer excellent experimental models for studies of multiple transmitters and their joint actions at uniquely identified nerve-muscle junctions. Peptidergic systems in insects are reviewed with particular reference to two identified neuromuscular preparations which demonstrate cotransmitter actions of peptides and "classical" neurotransmitter substances.

Animals↗
PubMedDate not supplied

Stochastic modeling of facilitated neurosecretion.

Two models of neurosecretion were evaluated in terms of their ability to predict the dependency of quantal content (m) on the frequency of repetitive stimulation of a lobster motoneuron. First, the hypothesis that neurosecretion is limited by a fixed number of release sites was tested by the fit of the distribution of m by uniform and nonuniform binomial statistics. The obtained release probabilities suggest that frequency facilitation can be due to activation of a group of sites with high release probabilities. However, the fit obtained using this model is not statistically significant due to a large number of fitting parameters. Second, the hypothesis that neurosecretion is limited by the rates of exchange between the releasable pool and the total store of quanta and that each stimulus enhances quantal mobilization was tested. Monte Carlo simulation was carried out in accordance with this model and reproduced the observed distribution of m with very few fitting parameters and therefore with a high level of significance (>0.1). This result demonstrates that mobilization of extra vesicles with each stimulus is a mechanism that allows a very accurate and parsimonious quantitative description of frequency facilitation.

Action Potentials↗