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Potential-dependent potassium currents in the rapidly adapting stretch receptor neuron of the crayfish.

The outward current was analysed in the rapidly adapting stretch receptor neuron of the crayfish Pacifastacus leniusculus with a two-micropipette potential clamp technique and K(+)-selective microelectrodes in an attempt to establish if the properties of this current could explain the difference in adaptive behaviour compared to the slowly adapting receptor. A fast activating outward current carried by K+ was revealed. The time constant of activation(tau n) was dependent on potential and had a mean value of 0.5 ms at potential steps to 0 mV. Activation followed a second-order process according to the Hodgkin-Huxley model. The potential dependence of activation (n infinity) followed by a sigmoid curve n infinity = 1/(1 + exp/[(E - En)/a]) with a half maximal activation potential En = -44 mV and a = -13 mV. When long pulses were applied the outward potassium current decreased with two time constants, one that was potential independent (0.2 s) and one that was potential dependent (2-8 s). The latter could be explained by accumulation of K+ in the extracellular space of the neuron. The potential dependence of inactivation followed a sigmoid function infinity = 1/(1 + exp[(E - Ek)/+a]) with Ek = -36 mV and a = 13 mV. The inactivation properties are different from those of the classical fast transient (IA) current. The transport system for the outward potassium current during depolarizing potential steps in the rapidly adapting stretch receptor is similar to the current found in the slowly adapting receptor neuron. However, the activation is faster and seems to occur at potentials more negative than in the slowly adapting receptor. These differences can contribute to but not entirely explain the difference in adaptive behaviour between the slowly and rapidly adapting receptor.

Action Potentials↗

The nature of the receptor mediating stimulant effects of histamine on rapidly adapting vagal afferents in the lungs.

1. The effects of histamine H1- and H2-agonists on these airway sensory receptors were also examined. 2. Neither I.V. infusion of metiamide (5 mg/kg, min for 35 min) in seven experiments, nor I.V. bolus injection of burimamide (15 mg/kg) in six other experiments, both substances being H2-antagonists, altered the response of rapidly adapting receptors to aerosols of histamine (from 0.1 or 1.0% solutions). 3. Chlorpheniramine (H1-antagonist), 2--5 mg/kg, I.V., completely abolished responses of rapidly adapting receptors to histamine in seven experiments in which metiamide had been given previously and in seven other preparations in which it had not, but had no effect on responses to prostaglandin F2 alpha. Chlorpheniramine itself caused a brief stimulation of rapidly adapting receptors. 4. The H2-agonist S-[3-(N,N-dimethylamino) propyl] isothiourea (Dimaprit), given as aerosol (1% solution for 2 min) or I.V. (2 mg/kg), was without effect on activity of four airway rapidly adapting receptors. These receptors were stimulated, however, by the H1-agonist 2,(2 pyridylethylamine) dihydrochloride (PEA), administered both as aerosol (from a 10% solution) and I.V. (0.4--2 mg/kg). These stimulant effects were abolished by chlorpheniramine. 5. The results indicate that stimulation of airway rapidly adapting receptors by histamine is mediated by histamine H1-receptors.

Animals↗

Morphology of pulmonary rapidly adapting receptor relay neurons in the rat.

The term rapidly adapting pulmonary stretch receptor (RAR) refers to one of the major pulmonary sensory receptors that responds to inflation and deflation of the lungs as well as to irritant stimuli with rapidly adapting irregular discharges. The functional role and central pathways are largely unknown. The aim of this study was to elucidate morphological characteristics of second-order neurons (RAR cells) activated by vagal afferent fibers originating from RARs. A mixture of horseradish peroxidase (HRP) and Neurobiotin was injected intracellularly into physiologically identified RAR cells in Nembutal-anesthetized, immobilized, and artificially ventilated Wister rats. Direct visualization of individual RAR cells (n = 12), including their somata, dendritic arborizations, and fine axonal branches with terminal boutons, was possible for the first time. Their somata were located in the commissural or medial subdivision of the nucleus of the solitary tract, caudal to the level of the area postrema. The RAR cells had, in addition to dendrites extending into the NTS area, one or two long dendrites extending laterally and/or ventrolaterally into the medullary reticular formation. The stem axons issuing from the RAR cells first coursed ventrolaterally toward the reticular formation in the vicinity of the ambiguus nucleus and then bifurcated into ascending and descending axons: three RAR cells possessed only ascending axons. Some of the ascending axons could be traced as far as the level of the facial nucleus and some of the descending axons beyond the spinomedullary junction. These ascending and/or descending axons gave off extensive axon collaterals distributing boutons within and in the vicinity of the ambiguus nucleus. These results, showing an anatomical substrate for the network implicated in RAR-evoked reflexes, provide useful clues for study of the RAR system.

Afferent Pathways↗

Projections from Pacinian corpuscles and rapidly adapting mechanoreceptors of glabrous skin to the cat's spinal cord.

1. Single axons innervating Pacinian corpuscles and rapidly adapting mechanoreceptors of the foot and toe pads were injected with horseradish peroxidase near their entrance to the lumbosacral spinal cord in cats anaesthetized with chloralose and paralysed with gallamine triethiodide. Subsequent histochemistry revealed the morphology of the intra-spinal parts of the axons. 2. All Pacinian corpuscle axons that could be traced into the dorsal root bifurcated upon entering the cord into ascending and descending branches. All Pacinian corpuscle axons gave rise to collaterals that entered the dorsal horn. 3. The collaterals of Pacinian corpuscle afferent fibres had a distinctive morphology. They provided two regions of termination, a larger dorsal region in laminae III and IV and a smaller ventral region in laminae V and VI. Within the dorsal region the terminal axons ran mainly in the longitudinal axis of the cord and carried many boutons en passant. Within the ventral region the axons ran dorso-ventrally in the transverse plane of the cord and although carrying some boutons en passant also gave rise to clusters of boutons. 4. The collaterals of rapidly adapting afferent fibres had a distinctive morphology different from that of the Pacinian corpuscle afferent fibre collaterals. The termination region of rapidly adapting afferents was limited almost exclusively to lamina III, with only slight extension into lamina IV. Boutons were mainly of the en passant type and terminal axons were generally orientated within the longitudinal axis of the cord. 5. The morphology of the afferent fibre collaterals is discussed in relation to the physiology of the dorsal horn.

Animals↗

Rapid adaptation of cardiac ryanodine receptors: modulation by Mg2+ and phosphorylation.

Channel adaptation is a fundamental feature of sarcoplasmic reticulum calcium release channels (called ryanodine receptors, RyRs). It permits successive increases in the intracellular concentration of calcium (Ca2+) to repeatedly but transiently activate channels. Adaptation of RyRs in the absence of magnesium (Mg2+) and adenosine triphosphate is an extremely slow process (taking seconds). Photorelease of Ca2+ from nitrophenyl-EGTA, a photolabile Ca2+ chelator, demonstrated that RyR adaptation is rapid (milliseconds) in canine heart muscle when physiological Mg2+ concentrations are present. Phosphorylation of the RyR by protein kinase A increased the responsiveness of the channel to Ca2+ and accelerated the kinetics of adaptation. These properties of the RyR from heart may also be relevant to other cells in which multiple agonist-dependent triggering events regulate cellular functions.

Adaptation, Physiological↗

On- versus off-responses of raccoon glabrous skin rapidly adapting cutaneous mechanoreceptors.

1. The on- and off-responses of 50 raccoon median nerve fibers associated with rapidly adapting cutaneous mechanoreceptors in glabrous skin were examined under experimental conditions designed to allow comparable opportunities for on- and off-responses to occur. Trapezoidal stimuli were utilized, providing for equal stimulus indentation and retraction velocities and equal static displacement times and intertrial intervals. Principal findings were as follows: 2. At stimulus levels well above displacement and velocity thresholds for on-responses, 80% of units yielded a more vigorous on-response than off-response (as measured by the total number of ramp impulses); in 6%, the reverse was true; while in the remaining 14%, the off-discharge was absent. 3. On and off displacement thresholds were approximately equal (on median, 43 micron; off median, 42 micron). However, on velocity thresholds were significantly lower than off velocity thresholds (on median, 1.0 micron/ms; off median, 3.8 micron/ms). 4. Exponents (b) of power functions relating discharge rate to ramp velocity (frequency = a x velocityb) were consistently greater for on-responses than for off-responses, but intercept constants (a) were consistently greater for off-responses than for on-responses. 5. Previous findings that mammalian rapidly adapting (RA) mechanoreceptors possess a "linear directionality" generally favoring on-responses were confirmed. 6. Results are discussed in relation to the role of viscoelastic properties of RA mechanoreceptors and neighboring skin. It is suggested that, when considerations is also given to the mechanical properties of surrounding tissues, the Loewenstein and Skalak (18) analysis of the mode of operation of Pacinian corpuscles might also apply, at least qualitatively, to the simple dermal (rapidly adapting) corpuscle of raccoon glabrous skin.

Afferent Pathways↗

A novel type of cold-sensitive neuron in rat dorsal root ganglia with rapid adaptation to cooling stimuli.

Cold sensing in mammals is heterogeneous and more than one type of receptor molecule is likely to be involved in the transduction process. Most features of innocuous cold receptors have been explained by TRPM8, the cold and menthol receptor, but their fast adaptation to cooling has not yet been reproduced in cellular systems. In this study we have used a newly developed system for applying fast thermal stimuli to dissociated dorsal root ganglia (DRG) neurons from young rats (150-200 g) in primary culture. We describe a novel type of cold-sensitive rat DRG neuron with rapid adaptation to cooling. These cells (4.3% of the total DRG population) do not express either TRPM8 or the other cold-activated TRP channel, TRPA1, and the epithelial sodium channel (ENaC) is not involved in their transduction. Increases in intracellular calcium induced by cooling in rapidly adapting neurons are caused by calcium entry. These neurons express a large and rapidly adapting cold-induced inward current with a time constant of adaptation in the seconds range, and may correspond to the rapidly adapting cold receptors described in vivo.

Adaptation, Physiological↗

Rapid adaptation to internal states as a coding strategy in visual cortex?

Adaptation is a prominent feature of biological neuronal systems. A common interpretation of adaptation in terms of function is that it provides flexibility for a neuronal system to perform well under varying external conditions, for example by adjusting the input/output relation of a sensory system with reference to the ensemble of stimuli the organism currently perceives. This interpretation, however, only applies if the time-scale of adaptation is slower than the time-scale at which the environment changes. Experimentally it is observed, however, that adaptation can be very rapid. Spike-frequency adaptation of cortical neurons, for example, occurs on a time-scale of approximately 100 ms. Here we show that those rapid adaptation processes can also be understood within the framework of information theory. We start with the hypothesis that neuronal codes are designed to optimize the information a neuronal representation conveys about an input stimulus for any increasing time window beginning with stimulus onset, and we show that this implies a rapid adaptation of the neuronal code on the time-scale of stimulus presentation. Adaptation, however, does not occur because the state of the environment changes. Rather it is a reaction to changes of the organisms own internal state, e.g. the level of noise in the neuronal representation. We apply this approach to a model of an orientation hypercolumn in the primary visual cortex, and predict that inter-columnar interactions should adapt on the time-scale of a typical fixation period ( approximately 300 ms).

Adaptation, Psychological↗

Lung inflation inhibits rapidly adapting receptor relay neurons in the rat.

Pulmonary slowly adapting receptors (SARs) and rapidly adapting receptors (RARs) are important components of various respiratory reflexes. In anesthetized, paralyzed and artificially ventilated rats, we found an inhibitory linkage from the former to the latter system at the level of their second-order relay neurons (P cells and RAR cells, respectively). Lung inflation which activates RARs as well as SARs suppressed RAR cell activity evoked by electrical stimulation of the vagus nerve. Intracellular recordings from RAR cells showed IPSPs locked to electrical stimulation of the ipsilateral and contralateral vagus nerves at an intensity just above the threshold for P cell activation. Activation of P cells with glutamate suppressed RAR cell firing. Since P cells project to the area of RAR cells, taken together, these results strongly suggest that P cells synaptically inhibit RAR cells.

Action Potentials↗

Stimulation of rapidly adapting pulmonary stretch receptors by pulmonary lymphatic obstruction in dogs.

The effects of pulmonary lymphatic obstruction and pulmonary venous congestion on the activities of slowly adapting receptors (SAR) and rapidly adapting receptors (RAR) of the airways were examined in anaesthetized, artificially ventilated dogs. In 11 out of 12 RAR (12 dogs) examined, pulmonary lymphatic obstruction for a period of 20 min produced a sustained significant increase in activity without a significant change in peak airway pressure and dynamic compliance. The activity remained significantly elevated even after the pulmonary lymphatic obstruction was released. This stimulus was without effect on the SAR (n = 5 dogs). Pulmonary venous congestion alone increased the RAR activity (n = 7 dogs) significantly without producing significant changes in airway mechanics. Lymphatic obstruction, when superimposed upon congestion, did not produce a further significant increase in activity. In four dogs the effect of pulmonary venous congestion (left atrial pressure increased from 7.6 +/- 1.7 to 16.3 +/- 2.7 mmHg) (1 mmHg = 133.3 Pa) on pulmonary lymphatic flow was examined. The procedure caused a significant increase in lymph flow. These results suggest that in the dog, the RAR activity is influenced by changes in the pulmonary extravascular space.

Adaptation, Physiological↗

Properties of rapidly adapting receptors of the airways in monkeys (Macaca mulatta).

The properties of rapidly adapting receptors (RARs) of the airways were examined in anaesthetised, artificially ventilated, paralysed and thoracotomised monkeys. The RARs were identified (i) by their rapid adaptation to a maintained inflation and forced deflation of the lungs and (ii) by their conduction velocity measurements. Right atrial (n = 17) and left atrial (n = 13) injections of histamine (10 micrograms/kg) stimulated the RARs. The stimulation was associated with an increase in peak intratracheal pressure. Right atrial injections of phenyl diguanide (n = 6, 10 micrograms/kg) and 5-hydroxytryptamine (n = 6, 10 micrograms/kg) did not produce a significant stimulation of the RARs. Administration of irritant vapours such as ammonia, (n = 12), cigarette smoke (n = 8), alcohol (n = 10), acetone (n = 10) and ether (n = 7), caused a significant stimulation of the RARs. This stimulation occurred in spite of a significant decrease or no change in peak intratracheal pressure. During mild degrees of pulmonary venous congestion produced by graded increments in mean left atrial pressure (+5 and +10 mmHg), there was a graded increase in RAR (n = 6) activity. The present study shows the existence of the RARs in the airways of the rhesus monkey. These receptors are stimulated (i) by administration of agents which cause bronchoconstriction (ii) by vapours which cause airway irritation and (iii) in conditions which cause an expansion of the extravascular space in airways.

Animals↗

The role of calcium in the rapid adaptation of an insect mechanoreceptor.

The femoral tactile spine of the cockroach is a rapidly adapting mechanoreceptor in which the response to a step displacement is a burst of action potentials lasting about 1 sec. This adaptation seems to occur during the encoding of action potentials from receptor current, since there is no evidence of adaptation in the receptor potential, and the adaptation can be demonstrated by direct electrical stimulation of the single sensory neuron in the spine. We have recently presented evidence for a calcium-activated potassium conductance in the tactile spine receptor neuron, although it was not directly linked to adaptation. Since this conductance could be involved in the rapid adaptation of the tactile spine neuron, we sought an association between adaptation and the entry of calcium ions into the cell. Adaptation in the tactile spine neuron was examined by direct electrical stimulation using a randomly fluctuating current followed by frequency-response analysis. The dynamic behavior was studied as a function of the concentration of calcium ions in the bathing solution, the presence of calcium channel blocking agents, or the divalent cation ionophore antibiotic A23187. No evidence could be found that entry of calcium ions into the cell has a major role in the sensory adaptation.

Adaptation, Physiological↗

[Properties of the mechanoreceptors of the nipple of the guinea pig mammary gland. (Rapidly adapting mechanoreceptor units)].

Two types of rapidly adapting mechanosensitive units have been found in skin of the teat of guinea--pig mammary gland (RA1 and RA2). They wee not both spontaneously active. RA1 and RA2 have no position response. The relation between average frequency of discharge and displacement velocity at a constant displacement amplitude was linear for RA1. With constant velocity displacements, frequency versus displacement curves assume a horizontal orientation of relatively low discharge frequencies and are then displaced upward as velocity increases for RA1. The number and frequency of afferent impulses of RA1 decreased during repeated ramp mechanical stimulation. Vibratory tuning points were in the range of 10--25 Hz for RA1. 20% of mechanosensitive units were RA2, which have a high velocity threshold and rarely produce more than 2--3 impulses to high velocity. The fatigue of RA2 is not prominent. RA1 were classed as the velocity detectors and RA2 as "transient" detectors.

Action Potentials↗

An invasive species induces rapid adaptive change in a native predator: cane toads and black snakes in Australia.

Rapid environmental change due to human activities has increased rates of extinction, but some species may be able to adapt rapidly enough to deal with such changes. Our studies of feeding behaviour and physiological resistance to toxins reveal surprisingly rapid adaptive responses in Australian black snakes (Pseudechis porphyriacus) following the invasion of a lethally toxic prey item, the cane toad (Bufo marinus). Snakes from toad-exposed localities showed increased resistance to toad toxin and a decreased preference for toads as prey. Separate laboratory experiments suggest that these changes are not attributable to learning (we were unable to teach naive snakes to avoid toxic prey) or to acquired resistance (repeated sub-lethal doses did not enhance resistance). These results strongly suggest that black snake behaviour and physiology have evolved in response to the presence of toads, and have done so rapidly. Toads were brought to Australia in 1935, so these evolved responses have occurred in fewer than 23 snake generations.

Adaptation, Physiological↗

Mechanisms by which histamine stimulates rapidly adapting receptors in dog lungs.

The stimulant effect of histamine on intrapulmonary rapidly adapting receptors was studied in anesthetized, paralyzed, artificially ventilated dogs, to determine whether it was dependent on contraction of airway smooth muscle. Single- or few-afferent fiber recordings were made from small strands dissected from the otherwise intact vagus nerve. Aerosols of histamine increased both receptor discharge and tracheal pressure (Pt). In 27 experiments, isoproterenol prevented the increase in Pt but not in receptor activity induced by histamine. In another 32 experiments, acetylcholine (ACh) increased Pt to a greater extent than did histamine, whereas histamine increased receptor discharge more than ACh. When given as aerosol directly to the vicinity of the sensory receptor via a fiber bronchoscope, histamine stimulated 12 receptors, whereas ACh and buffer solution did not. Isoproterenol reduced slightly the stimulant effect of locally applied histamine on 8 receptors. We conclude that smooth muscle contraction is not essential for stimulant effects of histamine on rapidly adapting receptors in dog lungs, and that histamine acts directly on the receptors to increase their activity.

Acetylcholine↗

Effect of carbon dioxide on the activity of slowly and rapidly adapting pulmonary stretch receptors in cats.

Single fiber activity from slowly and rapidly adapting pulmonary stretch receptors (PSR) was recorded from the left cervical vagus of anesthetized, open-chested and artificially ventilated cats. Reducing the end-tidal CO2 to low values did not affect the frequency of occurrence of higher threshold (HT) PSR. Occlusion of the left pulmonary artery (LPA) had no significant effect on the resting discharge of both HT and low threshold (LT) PSR. Cyclic ventilation with 8% CO2 in O2 reduced the activity of LT and HT receptors by similar amounts, irrespective of their anatomical location. After LPA occlusion, CO2 ventilation reduced markedly the activity of both type of PSR but to the greatest extent that of the HT receptors, the majority of which were located in the intrapulmonary airways. The CO2 depressant effect may not be due solely to changes in H+ concentration at the receptor level, since acetazolamide did not totally abolish the effect even though it significantly reduced it. Sustained inflation with 8% CO2 in O2 significantly reduced the activity of HT receptors in both the dynamic and static phases of inflation, but had no effect on the activity of LT receptors. Direct localization showed that the receptors which were more accessible to CO2 (all HT and one LT) were located in the lung parenchyma. In the case of rapidly adapting receptors, sustained inflations with CO2 gave inconsistent results. The results show clearly that, as in other mammalian species, the PSR activity in cats is also reduced by hypercapnia. The present study stresses the importance of localizing the PSR and making the observations separately on the two types of PSR, for there may be qualitative and quantitative differences.

Acetazolamide↗

Stimulation of rapidly adapting receptors in canine lungs by a single breath of cigarette smoke.

Inhalation of smoke generated from high-nicotine cigarettes frequently evoked an immediate augmented inspiration in conscious dogs (J. Appl. Physiol. 54: 562-570, 1983); this reflex response was believed to result from a stimulation of rapidly adapting receptors in the lungs. To test this hypothesis, we recorded the vagal afferent activity arising from the rapidly adapting receptors in the lungs and delivered 120 ml of high- and low-nicotine cigarette smoke separately in a single ventilatory cycle in 20 anesthetized open-chest and artificially ventilated dogs. These receptors were stimulated on the first breath of delivery of smoke generated by high-nicotine cigarettes; activity increased from a base line of 0.9 +/- 0.2 to a peak of 9.9 +/- 1.2 (SE) impulses/breath (n = 58). After three to six breaths when the receptors' discharge returned toward base-line activity, a delayed increase of activity emerged (peak activity = 3.4 +/- 0.6 impulses/breath, n = 58) in 32 of the 58 receptors studied and lasted for three to seven breaths. By contrast, only a mild stimulatory effect of low-nicotine cigarette smoke was found, either immediately or after a delay, in 15 of the 54 receptors studied. We conclude that rapidly adapting receptors are stimulated by a single breath of cigarette smoke and that nicotine is the primary stimulant agent.

Adaptation, Physiological↗

The ipsilaterally evoked olivocochlear reflex causes rapid adaptation of the 2f1-f2 distortion product otoacoustic emission.

The onset behavior of the distortion product otoacoustic emission (DPOAE) at 2f1-f2 in anesthetized cats was measured with temporal resolution finer than 70 ms. The amplitude of the DPOAE adapts after onset of the primary tones by as much as 6 dB for monaural stimulation and 10 dB when the primaries are presented binaurally. DPOAE adaptation consists of a large, rapid component, with a time constant of roughly 100 ms, and a small, slower component with a time constant of roughly 1000 ms. The rapid component disappears when only the crossed olivocochlear bundle (OCB) is cut, whereas the slow adaptation persists after complete OCB section. The loss of rapid adaptation upon OC section is accompanied by a concomitant increase in the steady-state amplitude of the DPOAE. Thus an intact OC reflex can significantly alter DPOAEs obtained during routine measurement. Rapid adaptation of the monaurally evoked 2f1-f2 DPOAE is probably mediated by reflex activity in ipsilaterally responsive OC neurons innervating outer hair cells. The effects of this ipsilateral reflex on DPOAE amplitudes are typically twice as large as those of the contralateral reflex, presumably because there are twice as many ipsilaterally responsive OC neurons. Tests for the ipsilateral OC reflex based on the phenomenon of rapid adaptation should be both feasible and useful in human subjects.

Acoustic Stimulation↗