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L D Partridge

Publications and source records attributed to L D Partridge.

At least 19 recordsLinked to original sources
PubMed1995

Action of diphenylamine carboxylate derivatives, a family of non-steroidal anti-inflammatory drugs, on [Ca2+]i and Ca(2+)-activated channels in neurons.

Ca(2+)-activated channels, including Ca(2+)-activated non-selective (CAN) channels and Ca(2+)-activated Cl- channels play important roles in regulating the electrical activity of neurons. No blockers of neuronal CAN channels have been previously reported. We used 2-electrode voltage clamping to measure membrane currents and fura-2 fluorescence imaging to measure [Ca2+]i in molluscan neurons. We show that the diphenylamine carboxylate derivative flufenamate (FFA), but not mefenamate or the parent compound, cause a transient increase in ICAN and a slow outward current, and a maintained increase in [Ca2+]i. We interpret this as a FFA-dependent release of Ca2+ from intracellular stores and Ca2+ influx, [Ca2+]i-dependent activation of the CAN and slow outward currents, and slow FFA-dependent channel block.

Animals↗
PubMed1994

Cytoplasmic Ca2+ activity regulation as measured by a calcium-activated current.

Calcium-activated non-selective cation (CAN) currents were activated by quantitative injections of Ca2+ into voltage clamped bursting neurons of the snails Helix aspersa or Helix pomatia. Membrane potential was held at the potassium equilibrium potential and CAN currents were fit with a rising and falling exponential function. Ca2+ transporters and pumps of the cell membrane, endoplasmic reticulum, and mitochondria were selectively blocked with pharmacological agents. Bath solutions containing 0 Na Ringers, chlorpromazine, Na3VO4, or thapsigargin did not significantly change the CAN current decay constants from those measured in Ringers. External 2,4-dinitrophenol or internal ruthenium red, however, significantly lengthened the CAN current decay constant. It is concluded that mitochondria are the most important sink for sub-membrane Ca2+ activity in the range necessary to effectively activate CAN currents.

2,4-Dinitrophenol↗
PubMed1994

Intracellular calcium signaling induced by thapsigargin in excitable and inexcitable cells.

Signaling between intracellular Ca2+ stores and cell membrane channels or transporters is important to Ca(2+)-based second messenger systems. Two hypotheses, the capacitative and the Ca(2+)-induced Ca(2+)-influx models have been proposed to explain aspects of this signaling. In this study, we examined the applicability of these models in neuroendocrine (PC12), neuronal (dorsal root ganglion), immune (spleen), and fibroblast (3T3) cells. We used thapsigargin (TPG) to deplete specific intracellular Ca2+ stores and to increase the cytoplasmic Ca2+ concentration ([Ca2+]), and Ca2+ free medium to prevent Ca2+ influx and lower cytoplasmic [Ca2+]. We demonstrate that, although TPG causes an increase of [Ca2+]i in all cells examined, the subsequent stimulation of Ca2+ influx varies from high in spleen, to moderate in 3T3 and PC12, to undetectable in DRG cells. All cell types exhibited Ca2+ influx when Ca2+ was added to the medium following an exposure to Ca(2+)-free medium. Without added provisions, the two aforementioned hypotheses are inadequate in explaining the TPG-induced Ca(2+)-influx in all cell types. These results support the hypothesis of the existence of unique Ca2+ channels or transporters in spleen cells that operate subsequent to TPG treatment and are distinct from the voltage-gated Ca2+ channels and Ca(2+)-activated non-selective cation channels present in excitable cells.

3T3 Cells↗
PubMed1994

Calcium-activated non-selective channels in the nervous system.

In the decade, since the first description of calcium-activated non-selective (CAN) channels in cardiac myocytes, pancreatic acini and neuroblastoma, this type of channel has been shown to have a ubiquitous distribution across a variety of tissues. Recently, their role in the function of cells of the nervous system has become better delineated. Because CAN channels pass depolarizing current, respond to cytoplasmic Ca2+ activity and do not inactivate, they are capable of producing maintained depolarization of neurons. This property endows upon CAN channels an important role in both physiological functions and pathological processes of the nervous system.

Animals↗
PubMed1993

Activation and modulation of calcium-activated non-selective cation channels from embryonic chick sensory neurons.

We have shown that calcium-activated non-selective (CAN) channels from embryonic chick sensory neurons are permeable to both Na+ and K+ and are not blocked by TTX, TEA, or 4-AP. These neuronal CAN channels are activated by sub-micromolar cytoplasmic Ca2+ with negative cooperativity. The effect of Ca2+ is to decrease the closed times of the channel with little effect on the time the channel remains open. Isolated neuronal CAN channels can be phosphorylated by cAMP-dependent protein kinase (PKA). The effect of phosphorylation is to shorten channel open time and to minimize the effect of Ca2+ on channel closed time.

Animals↗
PubMed1990

Modulation of calcium-activated non-specific cation currents by cyclic AMP-dependent phosphorylation in neurones of Helix.

1. Currents through calcium-activated non-specific cation (CAN) channels were studied in the fast burster neurone of Helix aspersa and Helix pomatia. CAN currents were activated by reproducible intracellular injections of small quantities of Ca2+ utilizing a fast, quantitative pressure injection technique. 2. External application of forskolin (10-25 microM), an activator of adenylate cyclase, caused the endogenous bursting activity of the cells to be replaced by beating activity. These same concentrations of forskolin reduced CAN currents reversibly to about 50%. 3. External application of IBMX (3-isobutyl-1-methylxanthine, 100 microM), an inhibitor of phosphodiesterase, the enzyme which breaks down cyclic AMP, reduced CAN currents reversibly to about 40%. 4. External application of the membrane-permeable cyclic AMP analogues 8-bromo-cyclic AMP and dibutyryl-cyclic AMP (100 microM) caused almost complete block of the CAN current. A marked reduction in the CAN current was also observed following quantitative injections of cyclic AMP (internal concentrations up to 50 microM) directly into the cells from a second pressure injection pipette. 5. Similar results were obtained with quantitative injections of the catalytic subunit (C-subunit) of the cyclic AMP-dependent protein kinase (internal concentrations 10(-4) units of enzyme) directly into the cells from a second pressure injection pipette. 6. Injection of the non-hydrolysable GTP analogue, GTP-gamma-S (internal concentrations 100 microM), which stimulates G-proteins, produced a prolonged increase in CAN current amplitude by as much as 300%. 7. External application of serotonin (100-200 microM) caused a transition from bursting to beating activity of the neurones and mimicked cyclic AMP's effects on CAN currents. Two other neurotransmitters, dopamine and acetylcholine, were not significantly effective in reducing CAN currents. 8. Injection of a peptide inhibitor of cyclic AMP-dependent protein kinase suppressed serotonin's action on bursting and on CAN current. 9. Our results indicate that CAN currents in Helix burster neurones are modulated by cyclic AMP-dependent membrane phosphorylation. They suggest that the physiological transmitter that induces this second messenger action is serotonin. The dual control of CAN channels by two second messengers, namely Ca2+ and cyclic AMP, has important functional implications. While Ca2+ activates these channels which generate the pacemaker current in these neurones, cyclic AMP-dependent phosphorylation down-regulates them, thereby resulting in modulation of neuronal bursting activity.

1-Methyl-3-isobutylxanthine↗
PubMed1989

The sequential-interval state space: a means of displaying temporal information in neuron firing.

Variability in neuronal firing exhibits sufficient uncertainty so that a simple average firing frequency code is probably inadequate for most nervous system signalling. Temporal patterns certainly play an important role in neuronal coding. We have used interval histogram and 3-dimensional sequential interval state space plots to investigate various common patterns of firing in neurons of the land snail, Helix aspersa. Typical firing patterns included random, highly regular, doublet, and burst firing. Individual neurons could be made to change their temporal firing pattern in response to changes in transmembrane currents, or temperature, or the application of convulsant drugs. In every instance, the sequential interval state space plot provided a more distinctive display of temporal pattern than did the more common interval histogram. State space plots were also investigated for evidence of a predicted chaotic attractor. In no instance was this type of state space plot observed.

Action Potentials↗
PubMed1987

Single Ca-activated cation channels in bursting neurons of Helix.

The depolarizing drive that maintains bursting in Helix neurons is carried by a long-lasting calcium-activated inward current. This current was studied using cell-attached and inside-out patches from the right parietal fast burster neuron of Helix pomatia. One population of unitary currents was inward at -50 mV and showed an increased probability of opening when Ca2+ was injected or when excised patches were bathed in solutions with 10(-7) to 10(-5) M free Ca2+ levels. Cell-attached patches (patch electrodes filled with 10(-7) M Ca2+ Ringer) had single channel conductances near 30 pS with reversal potentials near -20 mV; excised patches had similar conductances in symmetrical Na+ solutions and reversal potentials within a few millivolts of zero. Calculations, assuming a simple spherical cell, yield a channel density of only about 1/6 micron2. The increased channel opening probability characteristically persisted well beyond the duration of transient whole-cell inward current. We conclude from this that the later phase of Ca-activated inward currents is normally masked by outward currents.

Action Potentials↗
PubMed1987

Phenobarbital: a locus of action on spike broadening and potassium inactivation.

1. The effect of phenobarbital on frequency-dependent spike broadening and potassium inactivation was studied in snail neurons. 2. The amount of spike broadening was significantly depressed by the application of 10(-3) M phenobarbital but the time course of broadening was unaffected. 3. In voltage clamped neurons, this concentration of phenobarbital significantly depressed the amount of potassium current inactivation without altering its time constant. 4. A possible locus of phenobarbital's anticonvulsant action is through a decrease in synaptic efficacy resulting from a depression of presynaptic spike broadening.

Animals↗
PubMed1984

The effect of pentylenetetrazol on inward currents of non-bursting neurons and its role in plateau formation.

The epileptogenic drug, pentylenetetrazol (PTZ) produces paroxysmal depolarization shifts in molluscan neurons that are similar to PDSs seen at a mammalian epileptic focus. Most research on molluscan neurons indicates that PTZ acts by altering ionic somatic conductances. This study was carried out to investigate the effect of PTZ on inward currents in isolated neurons of the pond snail, Lymnaea stagnalis, and to investigate how these altered currents might lead to the production of PDSs. In concentrations from 10 to 60 mM, PTZ decreased maximum inward current conductance and shifted the inactivation and activation curves to the left with the former shift being consistently greater. There was no change in reversal potential or time constants for activation and inactivation of inward currents. The effects of the PTZ-induced alterations in the inward currents were studied by incorporating them along with alterations of outward currents seen in this and other studies in a computer model for molluscan neuronal firing. The composite model reproduced in large part the intermediate changes in electrical activity seen before the development of the PDS as well as the PDS.

Animals↗
PubMed1984

The effect of pentylenetetrazol on spike broadening and potassium inactivation.

The effect of the convulsant drug, pentylenetetrazol (PTZ) on spike broadening and potassium current inactivation was studied. PTZ was found to decrease the time taken for a cell to reach maximal broadening as well as causing a decrease in the total amount of broadening. Voltage clamp studies showed that in the presence of PTZ potassium current inactivated less but exhibited a faster time constant of inactivation. By exerting an effect on potassium inactivation and thereby spike broadening, PTZ may alter synaptic efficacy. Such an effect on synaptic efficacy may partially underlie the drug's convulsive activity.

Action Potentials↗
PubMed1982

The good enough calculi of evolving control systems: evolution is not engineering.

In evolved aggregates of accidentally invented elements, retained when statistically good enough to identify limitations of antecedent systems, survival value might favor operators incorporating aspects of, while not identical with, feedback, feedforward, state varible, and "homeostatic" control. Generally, simple organizational increments should predominate. After invention, an internal controller with readily modifiable rules could facilitate evolution of compound inventions, but criteria controlling rule changes would be only indirectly (probably imperfectly) survival referent. Consequent to combination of independent invention with indirect criteria and statistical acceptance, evolved control logic could be: both redundant and incomplete; good enough with malefic aspects; built of loosely linked or autonomous sublogics; and a source of good enough solutions from incomplete information. The partially explicit rules are defined more by rejections than by ratifications. Study of the result based on formal logic, engineering conventions, and familiar coordinate systems could conceive illegitimate illusions of understanding.

Biological Evolution↗
PubMed1980

Calcium independence of slow currents underlying spike frequency adaptation.

This study assessed the role of calcium in the activation of the slow potassium current responsible for spike frequency adaptation in molluscan neurons. Inward calcium currents were eliminated by using Co2+, Cd2+, or OCa2+ EGTA in the bathing solution. In each case adaptation was found to persist, as did the slow current believed to be responsible for adaptation. Injection of EGTA into neurons was also found not to block adaptation. This potassium current provides an example of a slow voltage-dependent potassium process which is independent of calcium influx.

Action Potentials↗
PubMed1980

Probability of peripheral interaction between motor units and implications for motor control.

Potential and importance of mechanical interactions between motor units are examined. Studies were conducted on simple physical models of systems of motor units assembled from separate muscles and driven with electrical stimulus. Two separate muscles were connected to move a common load to represent mechanically coupled motor units while avoiding other interactions present between natural units. Force, velocity, length, power, and work outputs of one unit were measured with and without stimulus to the other unit. Excitation of one unit modified all response measures in the other. The basis for these interactions appears equally applicable to real motor units. Consequently, unqualified use of such terms, which imply independence, as quantal, summation, and average unit response is not acceptable without qualification when referring to activity of motor units. It is argued that the effects of force-velicty and length-tension relationships will cause appreciable mechanical interaction between motor units. Therefore, central nervous system strategies for organization of motor control cannot depend on unchanging response of individual units, and the principle of superposition should not be assumed in analyses of motor activities. The nature of the interactions suggests that the total effect of a unit response may include a "negative force" phase, and also energy exchanges can be expected between motor units in some configurations.

Action Potentials↗
PubMed1979

Current-voltage relationships of repetitively firing neurons.

The current-voltage curves of repetitively firing neurons show non-linearities in the subthreshold region. Microsurgically isolated molluscan neuron somata were studied under voltage clamp using ramp voltage command signals. During the depolarizing 1/2 cycle a region of negative slope conductance was observed. Ion substitution experiments suggest that this results from non-inactivating or slowly inactivating Na+ and Ca2+ currents. The hyperpolarizing 1/2 cycle reveals a hysteresis effect which results at least in part from a Ca2+ activated 5+ current. Similar characteristics have been described in bursting neurons. Their occurrence in the non-bursting neurons studied here shows that they are not unique to this class of neurons and suggests that their primary contribution is to create electrical instability necessary for repetitive firing.

Animals↗