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Innervation of putative rapidly adapting mechanoreceptors by calbindin- and calretinin-immunoreactive primary sensory neurons in the rat.

Calbindin and calretinin are two homologous calcium-binding proteins that are expressed by subpopulations of primary sensory neurons. In the present work, we have studied the distribution of the neurons expressing calbindin and calretinin in dorsal root ganglia of the rat and their peripheral projections. Calbindin and calretinin immunoreactivities were expressed by subpopulations of large- and small-sized primary sensory neurons and colocalized in a majority of large-sized ones. The axons emerging from calbindin- or calretinin-immunoreactive neurons innervated muscle spindles, Pacini corpuscles and subepidermal lamellar corpuscles in the glabrous skin, formed palisades of lanceolate endings around hairs and vibrissae, and gave rise to intraepidermal nerve endings in the digital skin. Since most of these afferents are considered as rapidly adapting mechanoreceptors, it is concluded that calbindin- or calretinin-expressing neurons innervate particular mechanoreceptors that display physiological characteristics of rapid adaptation to stimuli.

Aging↗

The speciation of conger eel galectins by rapid adaptive evolution.

Many cases of accelerated evolution driven by positive Darwinian selection are identified in the genes of venomous and reproductive proteins. This evolutional phenomenon might have important consequences in their gene-products' functions, such as multiple specific toxins for quick immobilization of the prey and the establishment of barriers to fertilization that might lead to speciation, and in the molecular evolution of novel genes. Recently, we analyzed the molecular evolution of two galectins isolated from the skin mucus of conger eel (Conger myriaster), named congerins I and II, by cDNA cloning and X-ray structural analysis, and we found that they have evolved in the rapid adaptive manner to emergence of a new structure including strand-swapping and a unique new ligand-binding site. In this review article we summarize and discuss the molecular evolution, especially the rapid adaptive evolution, and the structure-function relationships of conger eel galectins.

Animals↗

Electrophysiological and pharmacological analysis of synaptic inputs to pulmonary rapidly adapting receptor relay neurons in the rat.

The information from pulmonary rapidly adapting stretch receptors (RARs) to the central nervous system (CNS) is relayed in the nucleus tractus solitarii (NTS). The second-order neurons in the NTS referred to as RAR cells have recently been shown to receive rhythmic inputs from the central respiratory system in addition to the main inputs from RAR afferents. The present study analyzed these synaptic inputs by intracellular recordings from RAR cells, and by extracellular recordings combined with local applications of neuroactive drugs to RAR cells, in Nembutal-anesthetized, paralyzed, and artificially ventilated rats. The intracellular analysis identified both excitatory postsynaptic potentials (EPSPs) elicited presumably by RAR afferents and inhibitory postsynaptic potentials (IPSPs) synchronous with central inspiratory activity. This inhibitory input, called I suppression, was the origin of respiratory modulation of RAR cell firing, and its time course suggested that some unidentified inspiratory neurons with an augmenting firing pattern were the source of the inhibition. The pharmacological analysis suggested the types of neurotransmitters used in these synaptic events. First, glutamate was shown to be the primary neurotransmitter at the synapse between RAR afferents and RAR cells. Iontophoretic applications of the non-NMDA glutamate antagonist, CNQX, abolished RAR cell firing almost completely in response to lung inflation and deflation and to electrical stimulation of the vagus nerve. Second, glycinergic inputs which inhibited RAR cells in the inspiratory phase were revealed by applications of the glycine antagonist, strychnine. That is, the I suppression was greatly diminished by applications of strychnine. Third, although applications of the GABA(A) receptor antagonist, bicuculline, had little effect on I suppression, bicuculline markedly increased the baseline firing of RAR cells. These results imply that the information path from RARs to the CNS is regulated at the level of RAR cells by phasically-acting glycinergic inhibition in the inspiratory phase and tonically-acting GABAergic inhibition; the results also provide new insights into the neuronal mechanisms of RAR-induced reflexes.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Influence of lung stiffness on rapidly adapting receptors in rabbits and cats.

We examined the response of rapidly adapting receptors (RARs) to changes in dynamic lung compliance (CDYN), recording vagal impulses in open-chest rabbits and cats with lungs ventilated at constant f and VT, and a positive end-expiratory pressure (PEEP) of 3-4 cm H2O. After hyperinflation to produce maximal CDYN, most RARs fired irregularly and sparsely (less than 1 impulse X sec-1). Reducing CDYN in steps by briefly removing PEEP progressively stimulated RARs during inflation, activity increasing sevenfold when CDYN was reduced by 40% (P less than 0.0001). Reducing CDYN also increased RAR responses to static lung inflation. RAR stimulation by decreasing CDYN was virtually unaltered by atropine and hence was largely independent of reflex changes in bronchomotor tone. RARs were also stimulated by increasing VT at constant f, but, expressed as a function of airway pressure, the afferent response was less than that to increased lung stiffness (1/CDYN); expressed as a function of 1/CDYN, however, the responses were similar. We conclude that RARs signal increases in the force required to expand the lung, and speculate that their excitatory influence helps to maintain VT as the lungs become stiffer.

Afferent Pathways↗

Activation of pulmonary rapidly adapting receptors does not induce bronchoconstriction in dogs.

Activation of pulmonary rapidly adapting receptors (RARs) is believed to constrict airways by a vagally mediated reflex. We tested this hypothesis in dogs anesthetized with sufentanil citrate. We ventilated both lungs separately at a positive end-expiratory pressure of 4 cmH2O. We stimulated RARs in one lung under three different conditions: 1) deflation of the lung; 2) decrease in lung compliance; and 3) aerosolization of methacholine. We monitored the airway pressure in the nonstimulated lung as an index for airway muscle tone and could not detect increases in the pressure swing under these conditions. On the other hand, electrical stimulation of the distal end of cervical vagus nerve increased the pressure swing bilaterally (ipsilateral dominant), suggesting that reflex response could be detected in our preparation. Moreover, deflation (or inflation) of either lung increased (or suppressed) diaphragmatic activity. The results indicate intact vagal afferents and central response in our preparation. We conclude that activation of RARs located below the carina does not induce bronchoconstriction by a centrally mediated reflex. If any effect is present, it appears to be small.

Aerosols↗

Effects of thromboxane A2 agonist STA2 on rapidly adapting pulmonary stretch receptors in vagotomized rabbits.

We investigated the responses of rapidly adapting pulmonary stretch receptors (RARs) and tracheal pressure (PT) to right atrial injections of the thromboxane A2 (TXA2) stable analogue STA2 (0.3, 1.0, and 3.0 microgram/kg) before and after administration of atropine sulfate (1 mg/kg), isoprenaline (200 micrograms/kg), indomethacin (1 mg/kg), or S-145 (0.5 mg/kg) in artificially ventilated, bilaterally vagotomized rabbits. The RARs increased their activity after STA2 administration, and the increase was dose-dependent. However, intraatrial injections of STA2 at all the doses examined had no significant effect on PT. The excitatory responses of RAR activity to STA2 (0.3-3.0 micrograms/kg) were not significantly altered by administration of atropine sulfate (anticholinergic agent), isoprenaline (bronchodilator), or indomethacin (cyclooxygenase inhibitor). However, S-145 treatment (TXA2 antagonist) blocked the STA2-induced RAR stimulation. To determine whether or not administration of STA2 causes release of acetylcholine (ACh), we also examined the effects of vagal efferent stimulation (10-15 V, 10 Hz, 1 ms), STA2 administration (3.0 micrograms/kg), and their combination on PT in rabbits associated with both artificial ventilation and bilateral vagotomy. The vagally mediated bronchoconstriction that led to an increase in PT was not enhanced by simultaneous administration of STA2 at 3.0 micrograms/kg in all of the tested animals. These results suggest that the stimulation of RARs by STA2 is not mediated by the release of ACh from the nerve endings but is probably due to a local inflammatory bronchoconstriction that does not significantly alter the value of PT.

Animals↗

[Functional characteristics of rapidly adapting mechanoreceptor units of the rat mammary gland nipple].

Two types of rapidly adapting mechanosensitive units were found in the teat of the rat mammary gland (RAI and RAII). Neither was spontaneously active. 10% of the units were RAII and had the functional characteristics of "transient" receptors. The relation between the average frequency of discharge and the velocity of displacement at a constant displacement amplitude was linear for RAI. The latency of the first spike decreased when indentation velocity increased. The number and frequency of afferent impulses decreased at a repeated mechanical stimulation. Vibratory tuning points were in the range 10--25 Hz for RAI. RAI units were not directionally sensitive to the teat displacement.

Action Potentials↗

Vibration sensitivity of slowly and rapidly adapting cutaneous mechanoreceptors in the human foot and leg.

The activities of 30 rapidly adapting cutaneous receptors (FA) and 23 slowly adapting cutaneous receptors (SA) were recorded from the lateral peroneal nerve using the microneurographic method. Their sensitivity to mechanical vibrations with constant amplitude applied at various frequencies to the center of the receptive field was studied. These two populations of cutaneous receptors were found to be very sensitive to this stimulus: they could be driven in a one to one manner up to between 100 and 200 Hz. The difference lay in the response observed when the vibration frequency was increased to above this critical value: the FA receptors sharply stopped firing, whereas the SA receptors became progressively unlinked from the stimulus. The effects of vibration on the physiological messages were also studied. The results showed that the messages coding the properties of tactile stimuli were either completely or partly masked by the receptor response to vibration. These vibration-induced modifications of cutaneous sensory messages might be at least partly responsible for the sensorimotor alterations observed when subjects are exposed to vibration.

Electrophysiology↗

Stimulation of pulmonary rapidly adapting receptors by inhaled wood smoke in rats.

1. The stimulation of pulmonary rapidly adapting receptors (RARs) by wood smoke was investigated. Impulses from seventy RARs were recorded in fifty-nine anaesthetized, open-chest and artificially ventilated rats; responses to delivery of 6 ml of wood smoke into the lungs were studied in sixty-one receptors whereas responses to histamine (10 or 100 microg kg-1, i.v.) were studied in the other nine. 2. Delivery of wood smoke stimulated fifty-two of the sixty-one RARs studied. When stimulated, an intense burst of discharge was evoked within 1 or 2 s of smoke delivery. This increased activity quickly peaked in 1-3 s (Delta = 15.8 +/- 1.6 impulses s-1; n = 61; mean +/- s.e.m.), then declined and yet remained at a level higher than the baseline activity. The mean duration of the stimulation was 25.1 +/- 2.7 s. In contrast, smoke delivery did not affect tracheal pressure. 3. Peak responses of RARs to wood smoke were partially reduced by removal of smoke particulates and were largely attenuated by pretreatment with dimethylthiourea (DMTU, a hydroxyl radical scavenger), indomethacin (Indo, a cyclo-oxygenase inhibitor), or both DMTU and Indo (DMTU + Indo). Conversely, the peak responses of RARs were not significantly affected by pretreatment with isoprenaline (a bronchodilator) or vehicle for these chemicals. Additionally, pretreatment with DMTU, Indo, or DMTU + Indo did not significantly alter the RAR sensitivity to mechanical stimulation (constant-pressure lung inflation; 20 cmH2O). 4. Of the nine RARs tested, six were stimulated by histamine and their sensitivity to this chemical irritant was not altered by pretreatment with DMTU + Indo. 5. The results suggest that both the particulates and gas phases are responsible for, and both the hydroxyl radical and cyclo-oxygenase products are involved in, the stimulation of RARs by wood smoke. Furthermore, changes in lung mechanics following smoke delivery are not the cause of this afferent stimulation.

Animals↗

Responses of rapidly adapting afferent neurons to dynamic stretch of rat hairy skin.

Twenty-four rapidly adapting (RA) cutaneous afferents were recorded from a preparation of isolated, innervated hairy skin from the rat hindlimb for the purpose of identifying the mechanical variables associated with the initiation of afferent discharge. Neurons were studied while the skin was stretched dynamically along a single direction with the use of a linear actuator and a feedback controller. Input signals were load- or displacement-controlled stretches that followed either periodic or pseudorandom Gaussian noise control signals. When the tissue was actuated, loads and displacements were measured along the direction of stretch and neuronal responses were recorded. All RA afferents were activated by dynamic stretching. None had a sustained response to static stretch. Cross-correlation products, calculated between neuronal responses and either stress- or strain-related variables observed at the time of the spike, revealed a strong relationship between neuronal responses and tensile stress. Neuronal responses were observed at rates of change of stress between +1,000 and -800 kPa/s. Neuronal responses were poorly related to skin strain. Two loading conditions were used along the direction transverse to the stretch. In one condition the sides were unconstrained, so that on axial loading there was zero stress and negative strain along the transverse axis. In the other condition the sides were constrained so that when the tissue was loaded axially there was zero strain and positive stress along the transverse axis. In these two conditions the same level of axial stress was associated with two levels of axial strain. The neuronal responses were determined by the stress and not the strain. Neuronal responses were observed at stresses >5 kPa. It appears that RA afferents make little contribution to signaling limb movements or position in rat hindlimb on the basis of the behavior of rat hindlimb skin, as observed when the limb is rotated.

Adaptation, Physiological↗

Tactile discrimination of shape: responses of rapidly adapting mechanoreceptive afferents to a step stroked across the monkey fingerpad.

Responses of rapidly adapting Meissner corpuscle mechanoreceptive afferent fibers (RAs) to steps of varying shape stroked across the distal fingerpad were recorded from anesthetized monkeys. A series of flat plates were used, each having an increase in thickness (a step) in the middle so that one-half of the plate was thicker than the other. The cross-sectional shape of the step approximated that of a half-cycle sinusoid, 0.5 mm high. The width (half-cycle wavelength) of the sinusoidal step was varied from 0 to 3.13 mm, producing a series of step shapes that differed in steepness and curvature. These steps could be broadly categorized into 2 groups, "steep" and "gradual." Each step was stroked back and forth under constant compressional force, using a servocontrolled mechanical stimulator. The RA's response to a step provided a spatial pattern of action potentials in which the occurrence of each impulse corresponded to a position of the step on the skin. This response consisted of a single "burst" of impulses to the sinusoidal portion of the step. Changes in stroke direction, step shape, or velocity of stroking primarily affected the RA discharge rate during the burst, and, less consistently, the spatial width of the burst. For a given step shape and stroke velocity, the discharge rate was greater for strokes from the low to the high side of the step than for strokes from the high to the low side. Discharge rate was greater for steep than for gradual steps and, for a given step, it increased with stroke velocity. All the major features of the responses were interpreted as being due predominantly to the sensitivity of the RA to vertical velocity at the most sensitive spot on its receptive field, together with a sensitivity to the rate of change in skin curvature at that spot. RA discharge rate distinguished not only the gross differences between steep and gradual steps, but also some of the finer differences in sharpness among steep steps. From a comparison with the human capacity for tactile discrimination of the steps, it was concluded that RAs, through their discharge rates, provide primarily "intensive" information about the sharpness of shapes.

Adaptation, Physiological↗

Stability of rapidly adapting afferent entrainment vs responsivity.

Spike discharge activity was recorded from low-threshold, rapidly adapting, skin mechanoreceptive afferents (RA afferents) dissected from the median (forelimb) or tibial (hindlimb) nerves in anesthetized monkeys and cats. The spike activity was evoked by delivery of controlled sinusoidal vertical skin displacement ("flutter") stimuli to the receptive field (RF). The stimuli (15-30 Hz; 30-400 microm peak-to-peak amplitude; duration 0.8-15 s) were superimposed on a static skin indentation (0.5-1.0 mm) which was either maintained continuously throughout the run or applied trial-by-trial. The neural activity and the analog signal of the position of the stimulator probe were digitized at 10 kHz resolution and stored for off-line analysis. The main goal was to determine whether changes in the RA afferent response to skin flutter stimulation may be responsible for the enhanced capacity to discriminate stimulus frequency that accompanies a relatively brief (approximately 1 min) pre-exposure to such stimulation in humans. To this end, the spike train data were evaluated using methods that enabled independent measurement of entrainment and responsivity. Responsivity (response intensity) was measured as the average number of spikes/stimulus cycle, while entrainment (the degree to which evoked spike train activity is phase-locked to the stimulus) was quantitatively assessed using statistical techniques developed for the analysis of "circular" (directional) data, supplemented by methods based on the calculation of power spectra from point process data. The methods are demonstrated to enable quantification of RA afferent entrainment over a range of stimulus durations and amplitudes substantially greater than reported in previous studies. While RA afferent responsivity was found to decline to a minor extent (10-20%) both across and within stimulus trials, entrainment remained consistently high and stable, and exhibited no temporal trends or dependence on any other measured factor. The average phase angle of the entrained RA afferent response also remained stable both within and across trials, showing only a tendency to increase slightly during the initial 100-500 ms after stimulus onset. The results imply that the improved capacity to discriminate stimulus frequency that develops in response to an exposure to cutaneous flutter stimulation is not attributable to a change in RA afferent entrainment per se.

Afferent Pathways↗

Action of histamine on the rapidly adapting airway receptors in the dog.

The effects of histamine on the activity of rapidly adapting receptors (RAR) of the airways were investigated in anesthetized dogs. With bolus injections given into the right atrium, the threshold dose of histamine required for the excitation of RAR (n = 7) was 0.82 microgram/kg (+1.33/-0.51, geometric mean). With increasing doses of histamine, a dose-response relationship was seen in the activity of RAR. Obstruction of the lymphatic drainage from the lungs reduced the threshold dose to histamine (i.e., shifted the dose-response curve to the left significantly). This change in the dose-response relationship was not accompanied by a corresponding change in the relationship of histamine dose to airway pressures recorded before and after lymphatic obstruction. Against a background of pulmonary venous congestion produced by partial obstruction of the mitral valve, subthreshold doses of histamine stimulated the RAR (n = 4). The excitatory effect of histamine on RAR was found to be abolished by the administration of the H1 receptor antagonist diphenhydramine but not by the H2 receptor antagonist cimetidine. Intravenous infusion of histamine (0.4 microgram.kg-1.min-1) for a period of 10 min increased the RAR activity (n = 6) significantly without producing detectable changes in airway mechanics. The results indicate that contraction of the smooth muscle of the airways may not be a prerequisite for the excitation of RAR, especially at low doses. It is suggested that some of the effects of histamine on RAR are mediated by a local expansion of the extravascular fluid caused by an increase in the permeability of the bronchial vasculature.

Action Potentials↗

Rapidly adapting receptors monitor lung compliance in spontaneously breathing dogs.

We examined the ability of rapidly adapting receptors (RARs) to monitor changes in dynamic lung compliance (Cdyn) in anesthetized spontaneously breathing dogs by recording RAR impulses from the vagus nerves. We decreased Cdyn in steps through the physiological range by briefly restricting lung expansion with an inflatable cuff around the chest and recording the response after deflating the cuff; we restored Cdyn to control by hyperinflating the lungs. Of 45 RARs, 34 were stimulated by a 40 +/- 2% reduction in Cdyn, their inspiratory discharge increasing on average more than threefold. Two-thirds of responsive RARs were stimulated by less than or equal to 20% reductions in Cdyn; in most, firing increased proportionately with lung stiffness (1/Cdyn) as Cdyn was decreased further. Stimulation by reduced Cdyn was not simply a function of the concomitant increase in transpulmonary pressure, because similar increases in pressure produced by increasing tidal volume produced smaller increases in firing. RAR stimulation was unaffected by atropine and, hence, was not dependent on neurally mediated changes in bronchomotor tone. Our results indicate that during spontaneous breathing RARs provide a signal inversely proportional to Cdyn.

Adaptation, Physiological↗

Mechanisms underlying stimulation of rapidly adapting receptors during pulmonary air embolism in dogs.

We investigated the mechanisms underlying stimulation of rapidly adapting receptors (RARs) during pulmonary air embolism (PAE). Impulses were recorded from RARs in 43 anesthetized, open-chest and artificially ventilated dogs. Forty one out of 56 RARs were stimulated by infusion of air into the right atrium (0.2 ml/kg per min for 10 min). As a group (n = 56), RAR activity increased from a baseline of 1.2 +/- 0.2 to a peak of 4.3 +/- 0.3 impulses/breath at 8-10 min after the onset of PAE induction. PAE also caused an increase in total lung resistance and a decrease in dynamic lung compliance. Studies were repeated in 33 RARs initially stimulated by PAE. In nine receptors, hyperinflation of the lungs performed at the termination of the second PAE induction largely reversed both the afferent and bronchomotor responses. Furthermore, the residual PAE-evoked activity subsequent to hyperinflation was almost eliminated by elevation in the heart position. In another 24 receptors, the responses of RARs to PAE were unaltered by pretreatment with saline (n = 8) or dimethylthiourea (a hydroxyl radical scavenger; n = 8), but was significantly attenuated by pretreatment with ibuprofen (a cyclooxygenase inhibitor: n = 8). These results suggest that: (1) the increased RAR activity following PAE is associated primarily with an increase in bronchomotor tone and secondarily with the mechanical action of the beating heart impacting on lung tissues; and (2) cyclooxygenase products may be involved in this sensory stimulation.

Afferent Pathways↗

Inspiratory inhibition of pulmonary rapidly adapting receptor relay neurons in the rat.

Second-order relay neurons (referred to as rapidly adapting pulmonary stretch receptors (RARs)-cells) activated by vagal afferents originating from RARs were identified electrophysiologically in Nembutal-anesthetized, paralyzed and artificially ventilated rats. Their location in the commissural subnucleus of the nucleus tractus solitarii (NTS) and firing properties in response to lung inflations and deflations were studied in detail for the first time in the rat. Importantly, in all the RAR-cells examined, their firing was suppressed to various extent during a period from inspiration to early expiration. This means that the information from the RARs to the central nervous system is gated by the central respiratory system at the level of RAR-cells in the NTS.

Action Potentials↗

Rapidly adapting receptors in a rabbit model of mitral regurgitation.

1. Unlike in normal rabbits, pulmonary rapidly adapting receptors (RARs) in rabbits with chronic mitral regurgitation (MR) do not respond to small changes in extravascular fluid (EVF) volume in major airways. The present study examined the effect of shrinking the EVF volume in rabbits with chronic MR by infusing hypertonic albumin, to see whether this response of RARs is restored. The effect of raising the left atrial pressure (LAP) acutely above 25 mmHg (to cause pulmonary oedema) on RARs was also investigated. 2. Mean RAR activities in rabbits with MR (n = 6) at initial control, LAP +5 mmHg, LAP +10 mmHg and final control periods were 20.9 +/- 9. 5, 18.8 +/- 11.3, 27.0 +/- 11.2 and 17.2 +/- 9.8 action potentials min-1, respectively (P > 0.05, ANOVA). After infusion of 35 % bovine serum albumin i.v. these values were 9.4 +/- 3.2, 30.6 +/- 14.6, 48. 9 +/- 10.1 and 18.4 +/- 7.3 action potentials min-1, respectively (P < 0.01, ANOVA). In rabbits with chronic MR (n = 7) raising the LAP above 25 mmHg stimulated RARs. 3. EVF content of the airways and lungs was measured in rabbits with MR and in control rabbits, at baseline and after elevation of the LAP by 10 or 25 mmHg for 20 min. In control rabbits the EVF contents in the lower trachea, carina and bronchi at baseline and at LAP +10 mmHg were 52.1 +/- 1.2 and 57.8 +/- 1.7 %, respectively (P < 0.05, Student's t test). In rabbits with MR these values were 58.3 +/- 1.5 and 56.9 +/- 1.9 %, respectively. When the LAP was elevated by 25 mmHg the EVF content increased to 62.4 +/- 1.1 % (P < 0.05, t test compared with baseline and LAP +10 mmHg). 4. We concluded that in rabbits with chronic MR, RARs are unable to respond to acute, small elevations of LAP because there is no concomitant increase in EVF content in the vicinity of these receptors. Furthermore, these receptors can be activated in these animals by elevating the LAP above 25 mmHg or can be made sensitive to acute small elevations of LAP by shrinking the chronically expanded EVF compartment.

Action Potentials↗

Transducer properties of the rapidly adapting stretch receptor neurone in the crayfish (Pacifastacus leniusculus).

1. The transducer properties of the rapidly adapting stretch receptor neurone of the crayfish (Pacifastacus leniusculus) were studied using a two-microelectrode voltage clamp technique. 2. The impulse response to ramp-and-hold extensions of the receptor muscle typically consisted of a high frequency burst followed by cessation of impulses within a relatively short time depending on the amplitude of extension. The type of adaptation was consistent with earlier studies. The stimulus-response relationship for the impulse frequency was non-linear and had a slope in a log-log plot of 2.9. 3. When impulse generation was blocked by tetrodotoxin (TTX), (block of Na+ channels) the receptor potential was extension dependent and similar to that found in the slowly adapting receptor. For small extensions there was an initial peak followed by a fall to a steady potential level. For large extensions the potential response during the ramp phase consisted of a peak followed by a constant potential level lasting to the end of the ramp. When the extension changed to the hold phase the potential fell towards a steady state. The relation between extension and amplitude of receptor potential was non-linear and saturated at -40 to -30 mV (extensions > 15% of zero length, lo). 4. When potassium channels were blocked by TEA (50 mM) and 4-aminopyridine (4-AP, 5 mM) (and Na+ channels blocked by TTX) the shape of the generator potential become less complex with an increased amplitude for large extensions. 5. When the receptor neurone was voltage clamped at the resting potential, extension of the receptor muscle produced an inwardly directed receptor current, the stretch-induced current (SIC). The response consisted of a fast transient phase which decayed towards a steady state. The SIC peak amplitude was dependent on extension in a sigmoidal fashion and saturated at 190 nA (extensions > 25% of lo). The slope of the steepest part of the stimulus-response relation (between 10 and 20% extension) was 4.7 +/- 0.25 (mean +/- S.E.M.) in a log-log plot. 6. The peak amplitude of the SIC increased with increasing extension speed (ramp steepness), the relation between the slope of the ramp and current amplitude being a first order (hyperbolic) function. The amplitude of the receptor current was voltage dependent and had a reversal potential of +16.2 +/- 1.8 mV (mean +/- S.E.M., 32 cells). From the reversal potential the permeability ratio, PNa/PK, of the transducer permeability system was calculated to be 1.5. The I-V curve of SIC was non-linear.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗