Biomedical subjects

A S French

Publications and source records attributed to A S French.

At least 37 records · Page 2Linked to original sources

PubMed1997

The efficiency of sensory information coding by mechanoreceptor neurons.

Most sensory systems encode external signals into action potentials for transmission to the central nervous system, but little is known about the cost or efficiency of this encoding. We measured the information capacity at three stages of encoding in the neurons of a spider slit-sense mechanoreceptor organ. For the receptor current under voltage clamp, the capacity was approximately 1400 bits/s, but when the neuron was allowed to generate a receptor potential, nonlinear membrane processes improved the capacity to >2000 bits/s. Finally, when action potentials were produced, the capacity dropped to approximately 200 bits/s, or approximately 14% of the receptor current capacity. These measurements provide a quantitative estimation of the cost of encoding analog signals into action potentials.

Action Potentials↗

PubMed1997

Ins(3,4,5,6)P4 specifically inhibits a receptor-mediated Ca2+-dependent Cl- current in CFPAC-1 cells.

We have examined the role of inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P4] in the control of Cl- current in CFPAC-1 cells. Intracellular Ins(3,4,5,6)P4 had no effect on basal current, but it produced a five- to sevenfold reduction in the Cl- current stimulated by either 2 microM extracellular ATP or by 1 microM extracellular thapsigargin. The half-maximally effective dose of Ins(3,4,5,6)P4 was 2.9 microM, and 4 microM blocked >80% of the ATP-activated current. In contrast, 10 microM Ins(1,4,5,6)P4, Ins(1,3,4,5)P4, or Ins(1,3,4,6)P4 enhanced rather than inhibited the ATP-activated Cl- current, although Ins(1,4,5,6)P4 only acted transiently. These stimulatory effects were Ca2+ dependent and largely inhibited by coapplication of equimolar Ins(3,4,5,6)P4. Inositol 1,3,4,5,6-pentakisphosphate, the precursor of Ins(3,4,5,6)P4, did not affect Cl- current. These data consolidate and extend the hypothesis that Ins(3,4,5,6)P4 is an important intracellular regulator of Cl- current in epithelial cells.

Adenosine Triphosphate↗

PubMed1997

Visual acuity for moving objects in first- and second-order neurons of the fly compound eye.

The early stages of visual systems contain a variety of components that limit both the spatial resolution and the temporal resolution of vision. When an animal sees a moving object, or moves relative to its environment, both spatial and temporal factors contribute to its ability to resolve the movement. In the present work we have combined currently available knowledge about the early stages of fly vision (optical system, photoreceptors, and large monopolar cells) to predict the resolution of the first two cell layers to moving point objects. These calculations included recent measurements of nonlinear light responses. Because background light level has a strong effect on the temporal behavior of these early visual layers, we examined the effects of light level on motion resolution. We also studied the effect of position within the eye, which is known to affect the static resolution of vision. Our results indicate that responses in large monopolar cells to moving point objects are maximal at angular velocities of 100-200 degrees/s. The resolution of point objects by both these early stages of the visual system is similar from stationary to an angular velocity of approximately 200 degrees/s. Above this, resolution deteriorates approximately linearly with velocity.

Animals↗

PubMed1997

Ionic selectivity of mechanically activated channels in spider mechanoreceptor neurons.

The lyriform slit-sense organ on the patella of the spider, Cupiennius salei, consists of seven or eight slits, with each slit innervated by a pair of mechanically sensitive neurons. Mechanotransduction is believed to occur at the tips of the dendrites, which are surrounded by a Na+-rich receptor lymph. We studied the ionic basis of sensory transduction in these neurons by voltage-clamp measurement of the receptor current, replacement of extracellular cations, and application of specific blocking agents. The relationship between mechanically activated current and membrane potential could be approximated by the Goldman-Hodgkin-Katz current equation, with an asymptotic inward conductance of approximately 4.6 nS, indicating that 50-230 channels of 20-80 pS each would suffice to produce the receptor current. Amiloride and gadolinium, which are known to block mechanically activated ion channels, also blocked the receptor current. Ionic replacement showed that the channels are not permeable to choline or Rb+, but are partly permeable to Li+. The receptor current was inward at all membrane potentials (-200 to +200 mV) and never reversed, indicating high selectivity for Na+ over K+. This situation contrasts strongly with insect mechanoreceptors, vertebrate hair cells, and mechanically activated ion channels in nonsensory cells, most of which are either unselective for monovalent cations or selective for K+.

Animals↗

PubMed1996

Information processing by graded-potential transmission through tonically active synapses.

Many neurons use graded membrane-potential changes, instead of action potentials, to transmit information. Traditional synaptic models feature discontinuous transmitter release by presynaptic action potentials, but this is not true for synapses between graded-potential neurons. In addition to graded and continuous transmitter release, they have multiple active zones, ribbon formations and L-type Ca2+ channels. These differences are probably linked to the high rate of vesicle fusion required for continuous transmitter release. Early stages of sensory systems provide some of the best characterized graded-potential neurons, and recent work on these systems suggests that modification of synaptic transmission by adaptation is a powerful feature of graded synapses.

Animals↗

PubMed1995

Characterization and regulation of a chloride channel from bovine tracheal epithelium.

1. The patch-clamp technique was used to characterize chloride channels from the apical membranes of bovine tracheal epithelial cells. Application of GTP gamma S or NaF to excised patches revealed the existence of a novel type of Cl- channel regulated by G-proteins in a membrane-delimited manner. 2. The channel had a linear current-voltage relationship, with a conductance of 100-120 pS. Its open probability was independent of voltage. 3. The channel was highly anion selective (permeability ratio, PNa/PCl = 0.06 +/- 0.04) and had the halide permeability sequence: I- > Br- > or = Cl- > F-, corresponding to the Eisenman I sequence. This suggested that neither ionic size nor diffusion rate determined ion permeation through the channel. 4. The mole fraction behaviour was studied using fluoride and chloride ions. Mixtures of ions produced currents that would be expected from the linear combination of the two ions acting independently, indicating relatively simple permeation through the pore and compatible with a single ion binding site. 5. The channel was inhibited by the stilbene disulphonates SITS (4-acetamido-4'-isothiocyanatostilbene-2, 2'-disulphonic acid) and DNDS (4,4'-dinitrostilbene-2,2'-sulphonic acid). SITS introduced voltage dependence to channel gating and indicated the possible involvement of lysine residues in the channel permeation pathway. 6. NaF was unable to activate Cl- channels in the presence of the aluminum chelator, deferoxamine mesylate. This indicates that Al3+ ions play an important role in chloride channel activation by fluoride. NaF activation was not dependent on the presence of calcium ions. 7. The channel was insensitive to alkaline phosphatase and to the specific inhibitors of protein phosphatase types I and 2A, okadaic acid and calyculin A. 8. The channels could be activated by GTP gamma S or by NaF in the presence of the phospholipase A2 inhibitor quinacrine, indicating that this enzyme is not involved in channel regulation.

Animals↗

PubMed1995

Evidence that pH-titratable groups control the activity of a large epithelial chloride channel.

The effects of pH changes were examined on the properties of a large, voltage dependent, epithelial Cl- channel from bovine tracheal cells. Alkaline solutions in the range pH = 7.4-9.2 had no detectable effects on channel conductance or gating. However, acid solutions significantly reduced channel open probability, raising the voltage required to open the channel. Analysis of channel activity in the acidic pH range suggested that at least one charged group on the channel with an apparent pK = 6.09, is responsible for its voltage dependence. Neutralization of this charge does not eliminate the voltage dependence, but changes the energy difference between the closed and open states. The absence of any change in channel conductance over this wide pH range suggests that the protonation site is far removed from the channel permeation pathway.

Animals↗

PubMed1995

Sodium channel distribution in a spider mechanosensory organ.

A site-directed antibody was used immunocytochemically to measure the distribution of sodium channels in the tissues of a spider mechanoreceptor organ. The VS-3 slit sense organ contains 7-8 pairs of bipolar sensory neurons; these neurons are representative of a wide range of arthropod mechanoreceptors. Sensory transduction is thought to occur at the tips of the dendrites and to cause action potentials that are regeneratively conducted to the cell bodies, although it has not been possible to confirm this by direct intracellular recordings from the dendrites. Wholemount preparations were labelled by immunofluorescence and thin sections were immunogold labelled, using an antibody to the highly conserved SP19 sequence of the voltage-activated sodium channel. Labelling for sodium channels was found in the neurons and in their surrounding glial cells. Both cytoplasm and membranes were labelled, but immunogold particles were clearly aligned along cell membranes, indicating that the majority of labelling represented membrane-bound sodium channels. Channel density in the dendrites was similar to the axons and higher than in the cell bodies, supporting the idea of active conduction in the sensory dendrites. Labelling in glial cell membranes was indistinguishable from the neighboring neurons, suggesting a significant role for sodium channels in the functions of these supporting cells.

Action Potentials↗

PubMed1995

Nonlinear neuronal mode analysis of action potential encoding in the cockroach tactile spine neuron.

Neuronal mode analysis is a recently developed technique for modelling the behavior of nonlinear systems whose outputs consist of action potentials. The system is modelled as a set of parallel linear filters, or modes, which feed into a multi-input threshold. The characteristics of the principal modes and the multi-input threshold device can be derived from Laguerre function expansions of the computed first- and second-order Volterra kernels when the system is stimulated with a randomly varying input. Neuronal mode analysis was used to model the encoder properties of the cockroach tactile spine neuron, a nonlinear, rapidly adapting, sensory neuron with reliable behavior. The analysis found two principal modes, one rapid and excitatory, the other slower and inhibitory. The two modes have analogies to two of the pathways in a block-structured model of the encoder that was developed from previous physiological investigations of the neuron. These results support the block-structured model and offer a new approach to identifying the components responsible for the nonlinear dynamic properties of this neuronal encoder.

Action Potentials↗

PubMed1995

Recording from cuticular mechanoreceptors during mechanical stimulation.

It is technically demanding to make intracellular measurements of mechanoreception in intact arthropod cuticular receptors. Here we introduce a method for recording mechanically induced electrical events in a class of spider mechanoreceptors using single electrode voltage- or current-clamp. A concave piece of cuticle containing a mechanosensitive lyriform slit organ was dissected free and fixed with wax onto a specially designed holder. This holder-cuticle complex, filled with spider saline, allowed displacement of the slit membrane from below while simultaneously recording intracellularly from neurons of the organ through a thin saline film. Extracellular ion concentrations could be changed and ion channel blockers could be applied to the bath. The method promises to allow the investigation of the ion channels responsible for mechanically transduced receptor signals and spike encoding.

Animals↗

PubMed1995

Slowly inactivating outward currents in a cuticular mechanoreceptor neuron of the cockroach (Periplaneta americana).

1. Although rapid adaptation is a widespread feature of sensory receptors, its ionic basis has not been clearly established in any touch receptor, because their small sizes have severely restricted the range of experiments tat can be performed. In the cockroach tactile spine, intracellular voltage-clamp recordings are now possible. 2. The basic electrophysiological properties of the cockroach femoral tactile spine neuron were studied using discontinuous (switching) single-electrode current- and voltage-clamp recordings. A slowly inactivating voltage-sensitive K+ outward current was detected after the major inward currents were blocked with tetrodotoxin. 3. The total outward current activated in < 1 ms at voltages above 0 mV. At moderate depolarizations it did not inactivate, but at higher depolarizations an inactivation time constant of approximately 260 ms was measured. Some recordings also revealed an additional, slower inactivation time constant of approximately 2.5 s. 4. More than half of the voltage-sensitive K+ outward current could be blocked with the Ca2+ channel blockers Co2+ and Cd2+. Tetraethylammonium chloride (TEA) also reduced the amplitude of the outward current to about half of its original amplitude. The actions of both blockers were reversible and probably reflect overlapping blockades of two separate outward currents. 5. The reversal potentials of the currents that remained after block with Co2+ (-91.7 mV) or TEA (-86.8 mV) were both near the K+ equilibrium potential expected for the tactile spine neuron. The voltage dependencies of activation of the Co(2+)- and TEA-resistant currents were both well fitted by Boltzmann distributions, giving values of half maximal activation (V50) equal to -34.5 mV for the Co(2+)-resistant current and -51.3 mV for the TEA-resistant current. 6. Current-clamp recordings revealed that the TEA-sensitive K+ current was the major component of action potential repolarization but that it did not effect the frequency of action potentials evoked by steady depolarization. On the other hand, blockers of Ca(2+)-sensitive K+ currents (Cd2+, Co2+, or charybdotoxin) reduced adaptation and increased the frequency of action potentials significantly but did not effect the duration or amplitude of individual action potentials.

Animals↗

PubMed1995

Transduction and adaptation in spider slit sense organ mechanoreceptors.

1. Mechanoreceptor neurons in spider (Cupiennlus salei) slit sense organ were examined by intracellular current- and voltageclarry recordings. Steps and pseudorandomly modulated displacement stimuli were delivered to the mechanosensitive cuticular slits. The resulting responses were used to determine the response dynamics and signal-to-noise ratio (SNR) of mechanoelectrical transduction. 2. Neurons were separated into two groups that, in terms of their afferent discharges, displayed different adaptations to displacement stimuli. Both responded at the onset of the step but then adapted fully, either immediately or within 10-200 ms. Voltage-clamp recordings showed only small differences in the receptor currents of the two groups. 3. Displacement of the slit caused a large inward current that decayed in seconds to a steady level of approximately 10-25% of the initial transient. When adapted to a steady displacement, the neurons responded to superimposed displacements in the same direction with additional transient currents, whose decay could be fitted by two exponentials with time constants of approximately 10 and 100 ms. In contrast, displacement in the opposite direction caused small "outward" currents without obvious adaptation. This behavior persisted with increasing background displacements, suggesting a shift in the displacement-response curve along the displacement axis. 4. White noise stimulation supported the step data and confirmed that the receptor's sensitivity was independent of mean slit membrane displacement. When the relative displacement of the stimulus (i.e., strain) was held constant at different maintained backgrounds, the SNR of the neurons remained fairly constant at approximately 2-10 over the frequency range from 4 to 450 Hz. The receptor current frequency responses showed high-pass characteristics, with a two- to sevenfold enhancement of the response amplitude and a phase lag relative to the stimulus of 90 degrees at 300 Hz. Low coherence values in the frequency range of 0.5-125 Hz were explained by nonlinear adaptation. 5. We conclude that, by rapidly adapting to the mean displacement of the slit membrane, slit organ mechanoreceptor neurons maintain a high sensitivity and SNR that allow the detection of small and rapid changes in cuticular strain.

Acoustic Stimulation↗

PubMed1995

Nonlinear models of the first synapse in the light-adapted fly retina.

1. Randomly modulated light stimuli were used to characterize the nonlinear dynamic properties of the synapse between photoreceptors and large monopolar neurons (LMC) in the fly retina. Membrane potential fluctuations produced by constant variance contrast stimuli were recorded at eight different levels of background light intensity. 2. Representation of the photoreceptor-LMC input-output data in the form of traditional characteristic curves indicated that synaptic gain was reduced by light adaptation. However, this representation did not include the time-dependent properties of the synaptic function, which are known to be nonlinear. Therefore nonlinear systems analysis was used to characterize the synapse. 3. The responses of photoreceptors and LMCs to random light fluctuations were characterized by second-order Volterra series, with kernel estimation by the parallel cascade method. Photoreceptor responses were approximately linear, but LMC responses were clearly nonlinear. 4. Synaptic input-output relationships were measured by passing the light stimuli to LMCs through the measured photoreceptor characteristics to obtain an estimate of the synaptic input. The resulting nonlinear synaptic functions were well characterized by second-order Volterra series. They could not be modeled by a linear-nonlinear-linear cascade but were better approximated by a nonlinear-linear-nonlinear cascade. 5. These results support two possible structural models of the synapse, the first having two parallel paths for signal flow between the photoreceptor and LMC, and the second having two distinct nonlinear operations, occurring before and after chemical transmission. 6. The two models were cach used to calculate the synaptic gain to a brief change in photoreceptor membrane potential. Both models predicted that synaptic gain is reduced by light adaptation.

Adaptation, Ocular↗

PubMed1994

The time course of sensory adaptation in the cockroach tactile spine.

Power-law dynamics have been widely used to fit the adaptation of sensory receptors, including the cockroach tactile spine. We used a new log-binning technique to re-examine step responses in the tactile spine. The power-law only fitted responses over a restricted time period, while a sum of three exponential decays gave an accurate fit over the entire response duration.

Acclimatization↗

PubMed1994

Evidence that channels below 1 pS cause the volume-sensitive chloride conductance in T84 cells.

The volume-activated chloride current of T84 human colonic cells was studied using the whole-cell patch clamp. The current appeared reliably with a mild osmotic gradient and in the absence of intracellular ATP. It reversed at the chloride equilibrium potential and was blocked by the chloride channel blocker DIDS. Development of the current was accompanied by an increase in the current noise variance, typical of increasing ion channel open probability. Noise variance was always well-fitted by a double Lorentzian relationship with corner frequencies at approximately 1.7 Hz and approximately 60 Hz. The increase in variance during development of the volume-sensitive current was mostly due to an increase in the high frequency component. The relationship between noise variance and membrane current was well-fitted by a relationship with a single channel conductance of approximately 0.2 pS.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1994

A nonlinear model of step responses in the cockroach tactile spine neuron.

Rapid sensory adaptation in the cockroach tactile spine neuron has previously been associated with a labile threshold for action potentials, which changes with the membrane potential by a process involving two time constants. A feed-forward, variable-threshold model has previously been used to account for the frequency response function of the neuron when stimulated with small-signal, white-noise currents. Here, we used a range of accurately controlled steps of extracellular current to stimulate the neuron. The same model was able to predict the individual step responses and could also fit the entire set of step responses from a single neuron if an initial, saturating, static nonlinearity was included. These results indicate that the two-time-constant, variable-threshold model can account for most of the rapidly adapting behavior of the tactile spine neuron.

Animals↗

PubMed1994

Characterization of a transient outward current in a rapidly adapting insect mechanosensory neuron.

This paper describes the first voltage-clamp recordings from an arthropod cuticular sensory neuron. In the femoral tactile spine neuron of the cockroach Periplaneta americana, a rapidly activating and inactivating outward current, IA, appeared when the neuron was hyperpolarized for a short period before a depolarizing test pulse. IA could be separated from the other outward currents using 5 mM 4-aminopyridine (4-AP), which specifically blocked it. Tetraethylammonium (TEA), (50 mM) did not remove IA, but decreased the steady-state outward current by about 50%. The threshold for IA activation was about -75 mV. The minimum activation and inactivation time constants were approximately 0.2 ms and 15 ms, respectively. The voltage dependencies of activation and inactivation were well fit-ted by Boltzmann distributions, giving values of membrane potential at half-maximal activation (V50) equal to -56.5 mV and an equivalent gating charge of n = 3.9 for activation and V50 = -86.7 mV and n = 3.4 for inactivation. In current-clamp recordings, 4-AP reversibly reduced the cell's normal adaptation by lowering the threshold for action potentials, but did not affect the amplitude or duration of single action potentials. These results indicate that IA plays a role in short-term adaptation by opposing membrane depolarization and reducing the spike frequency during maintained stimulation.

4-Aminopyridine↗

PubMed1994

Intracellular characterization of identified sensory cells in a new spider mechanoreceptor preparation.

1. We have developed an isolated mechanoreceptor-organ preparation in which the intact sensory structures are available for mechanical stimulation and electrical recording. The anterior lyriform slit sense organ on the patella of the spider, Cupiennius salei Keys., consists of seven or eight cuticular slits, each innervated by a pair of large bipolar sensory neurons. The neurons are fusiform, and the largest somata are < or = 120 microns long. The innervation of the organ was characterized by light microscopy of neurons backfilled with neuronal tracers. Intracellular recording was used to measure the passive and active electrical properties of the neurons, in several cases followed by identification with Lucifer yellow injection. Both neurons of each pair from one slit responded with action potentials to depolarization by a step current injection. Approximately half of the sensory neurons adapted very rapidly and generated only one or two action potentials in response to a sustained depolarizing step, while a second group produced a burst of action potentials that adapted to silence in approximately 1 s or less. Recordings from identified neuron pairs indicated that each pair consists of one rapidly adapting and one bursting neuron. Measurements of cell membrane impedances and time constants produced estimates of neuronal size that agreed with the morphological measurements. This new preparation offers the possibility of characterizing the mechanisms underlying transduction and adaptation in primary mechanosensory neurons.

Animals↗