电刺激家兔迷走神经中枢端诱导的黑-伯反射中的非联合型学习现象

本文旨在研究电刺激家兔迷走神经诱导的黑-伯（Hering-Breuer,HB）反射中的学习和记忆现象。选择性电刺激家兔迷走神经中枢端（频率10～100Hz,强度20～60μA,波宽0．3ms,持续60s）,观察对膈神经放电的影响。以不同频率电刺激家兔迷走神经可模拟HB反射的两种成分,即类似肺容积增大所致抑制吸气的肺扩张反射和类似肺容积缩小所致加强吸气的肺萎陷反射。（1）长时高频（≥40Hz,60s）电刺激迷走神经可模拟呼吸频率减慢,呼气时程延长的肺扩张反射。随着刺激时间的延长,膈神经放电抑制的程度逐渐衰减,表现为呼吸频率的减慢（主要由呼气时程延长所致）在刺激过程中逐渐减弱或消失,显示为适应性或“习惯化”的现象;刺激结束时呼吸运动呈现反跳性增强,表现为一过性的呼气时程缩短,呼吸频率加快,然后才逐渐恢复正常。长时低频（〈40Hz,60s）电刺激迷走神经可模拟呼吸频率加快、呼气时程缩短的肺萎陷反射。随着刺激时间的延长,膈神经放电增强的程度逐渐衰减,同样表现出“习惯化”现象;刺激结束后,膈神经放电不是突然降低,而是继续衰减,表现为呼气时程逐渐延长,呼吸频率逐渐减慢,直至恢复到前对照水平,表现了刺激后的短时增强效应。（2）HB反射的适应性或“习惯化”程度反向依赖于刺激强度和刺激频率,表现为随着刺激强度和频率的增加,膈神经放电越远离正常基线水平,即爿惯化程度减弱。结果表明,家兔HB反射具有“习惯化”这一非联合型学习现象,反映与其有关的呼吸神经元网络具有突触功能的可翅性,呼吸的中枢调控反射具有一定的适应性。     

Acetaldehyde affects mammalian neuromuscular transmission without observable postsynaptic effects.

Acetaldehyde, the first metabolite of ethanol, caused a reversible block of the end-plate potential (EPP) in the rat and mouse phrenic nerve--hemidiaphragm preparation. Decrease and block of the EPP occurred over a bath concentration range from 3 to 25 mM. The phrenic nerve compound action potential was blocked along with the EPP, and this block was not reversed by high bath Ca2+ concentration. The muscle action potential was unaffected even at concentrations up to 50 mM. Over the same concentration range (3--25 mM), miniature end-plate potential (MEPP) frequency sometimes decreased a few minutes after application, and over the ensuing 10--20 min would steadily increase to as much as 11 times the base-line frequency, particularly with higher doses. However, the shape of averaged MEPPs remained unchanged after acetaldehyde application, suggesting that this aldehyde does not have post-synaptic effects.     

The origin of the muscle fasciculation caused by funnel-web spider venom

The origin of the fasciculation of skeletal muscle produced by funnel-web spider venom (FSV) has been examined in mouse phrenic nerve hemi-diaphragm preparations, FSV from male spiders at concentrations greater than 10(-6) g/ ml invariably produced muscle fasciculation which could be prevented by d-tubocurarine (14micron), tetrodotoxin (0.3 micron) or by increasing the external magnesium concentration or calcium concentration. Diphenyl hydantoin (3-6 X 10(-5) M) was able to reduce these fasciculations in some experiments. In curarized preparations, multiple end plate potentials (EPPs) in response to single stimuli and bursts of spontaneous EPPs were seen in the presence of FSV (10(-5) g/ml). Extracellular recordings from phrenic nerves in the presence of FSV (10(-5) g/ml) revealed additional components in compound action potentials elicited by single stimuli, and "spontaneous" electrical activity was observed in unstimulated nerves. This spontaneous activity was abolished by raising the divalent cation concentration in the bathing solution. These results suggest that a primary site of action of FSV is the surface membrane of nerve fibres and that muscle fasciculation arises as a consequence of spontaneous action potentials produced by the venom in motor nerves.     

Inspiratory rhythm in airway smooth muscle tone

In anesthetized paralyzed open-chested cats ventilated with low tidal volumes at high frequency, we recorded phrenic nerve activity, transpulmonary pressure (TPP), and either the tension in an upper tracheal segment or the impulse activity in a pulmonary branch of the vagus nerve. The TPP and upper tracheal segment tension fluctuated with respiration, with peak pressure and tension paralleling phrenic nerve activity. Increased end-tidal CO2 or stimulation of the carotid chemoreceptors with sodium cyanide increased both TPP and tracheal segment tension during the increased activity of the phrenic nerve. Lowering end-tidal CO2 or hyperinflating the lungs to achieve neural apnea (lack of phrenic activity) caused a decrease in TPP and tracheal segment tension and abolished the inspiratory fluctuations. During neural apnea produced by lowering end-tidal CO2, lung inflation caused no further decrease in tracheal segment tension and TPP. Likewise, stimulation of the cervical sympathetics, which caused a reduction in TPP and tracheal segment tension during normal breathing, caused no further reduction in these parameters when the stimulation occurred during neural apnea. During neural apnea the tracheal segment tension and TPP were the same as those following the transection of the vagi or the administration of atropine (0.5 mg/kg). Numerous fibers in the pulmonary branch of the vagus nerve fired in synchrony with the phrenic nerve. Only these fibers had activity which paralleled changes in TPP and tracheal tension. We propose that the major excitatory input to airway smooth muscle arises from cholinergic nerves that fire during inspiration, which have preganglionic cell bodies in the ventral respiratory group in the region of the nucleus ambiguus and are driven by the same pattern generators that drive the phrenic and inspiratory intercostal motoneurons.     

Changes in strength of lung inflation reflex during prolonged inflation.

Recovery from respiratory inhibition produced by the lung inflation reflex was studied in anesthetized dogs, paralyzed and ventilated with a respiratory pump. During constant ventilation the lungs were periodically inflated using positive end-expiratory pressure, while the respiratory motor output was monitored in the phrenic nerve. Inhibition of the phrenic discharge was followed by gradual recovery throughout 8-min inflation periods despite constant blood gases. Recording afferent potentials in a vagus nerve indicated that adaptation of pulmonary stretch receptors contributed to the initial recovery of the phrenic discharge, but this recovery continued after the receptor discharge had stabilized. The phrenic discharge also recovered after initial inhibition in two situations which avoided stretch receptor adaptation: a) when the stretch receptor discharge from the separate lungs was alternated in an overlapping manner by asynchronous pulmonary ventilation, and b) during continuous electrical stimulation of a vagus nerve. Phrenic activity was temporarily increased above its control value after periods of lung inflation, asynchronous ventilation and vagal stimulation. It is concluded that the lung inflation reflex gradually attenuates during prolonged stimulation due to both stretch receptor adaptation and changes within the central pathways.     

Phosphoinositide metabolism in rat superior cervical ganglion, vagus and phrenic nerve: effects of electrical stimulation and various blocking agents

Abstract— Paired vagus nerves, phrenic nerves or superior cervical ganglia from rats were incubated at 37 C for various times in a simple salt solution containing glucose and ³²P_i. One of the pair was usually stimulated electrically for 30 or 60 min. Stimulation of vagus nerve for 30 min increased phosphate incorporation into all the phospholipids studied but the increase was significant only in the case of triphos-phoinositide and diphosphoinositide. This increase was not accompanied by increased labelling of the nucleotide labile phosphate pool. Tetrodotoxin at concentrations sufficient to block transmission had no effect upon phospholipid labelling in vagus or phrenic nerve. Ouabain at blocking concentration did not affect polyphosphoinositide metabolism in vagus nerve but increased [³²P]labelling of the other phospholipids. Hemicholinium-3 increased the labelling of all three phosphoinositides in the sympathetic ganglia but the increase in phosphatidylinositol labelling due to electrical stimulation was not seen in the presence of this inhibitor.     

Partial Recovery of Respiratory Function and Diaphragm Reinnervation following Unilateral Vagus Nerve to Phrenic Nerve Anastomosis in Rabbits

Respiratory dysfunction is the leading cause of mortality following upper cervical spinal cord injury (SCI). Reinnervation of the paralyzed diaphragm via an anastomosis between phrenic nerve and a donor nerve is a potential strategy to mitigate ventilatory deficits. In this study, anastomosis of vagus nerve (VN) to phrenic nerve (PN) in rabbits was performed to assess the potential capacity of the VN to compensate for lost PN inputs. At first, we compared spontaneous discharge pattern, nerve thickness and number of motor fibers between these nerves. The PN exhibited a highly rhythmic discharge while the VN exhibited a variable frequency discharge pattern. The rabbit VN had fewer motor axons (105.3±12.1 vs. 268.1±15.4). Nerve conduction and respiratory function were measured 20 weeks after left PN transection with or without left VN-PN anastomosis. Compared to rabbits subjected to unilateral phrenicotomy without VN-PN anastomosis, diaphragm muscle action potential (AP) amplitude was improved by 292%, distal latency by 695%, peak inspiratory flow (PIF) by 22.6%, peak expiratory flow (PRF) by 36.4%, and tidal volume by 21.8% in the anastomosis group. However, PIF recovery was only 28.0%, PEF 28.2%, and tidal volume 31.2% of Control. Our results suggested that VN-PN anastomosis is a promising therapeutic strategy for partial restoration of diaphragm reinnervation, but further modification and improvements are necessary to realize the full potential of this technique.     

Analysis of postinspiratory activity of phrenic motoneurons with chemical and vagal reflexes

We examined the effects of chemical and reflex drives on the postinspiratory inspiratory activity (PIIA) of phrenic motoneurons using a single-fiber technique. Action potentials from "single" fibers were recorded from the C5 phrenic root together with contralateral mass phrenic activity (also from C5) in anesthetized, paralyzed, and artificially ventilated cats with intact vagus and carotid sinus nerves. Nerve fibers were classified as "early" or "late" based on their onset of discharge in relation to mass phrenic activity during hyperoxic ventilation. Only the early fibers displayed PIIA but not the late fibers, even when their activity began earlier in inspiration with increased chemical drives. Isocapnic hypoxia increased, whereas hyperoxic hypercapnia shortened the duration of PIIA. Pulmonary stretch and "irritant" receptors inhibited PIIA. Hypercapnia and stimulation of peripheral chemoreceptors by lobeline excited both early and late units to the same extent, but hypoxic ventilation had a less marked excitatory effect on late fiber activity. Irritant receptor activation increased the activity of early more than late fibers. Hyperoxic hyperventilation eliminated late phrenic fiber activity, whereas early fibers became tonically active. Bilateral vagotomy abolished this sustained discharge in eight of nine early units, suggesting the importance of vagal afferents in producing tonic firing during hyperventilation. These results suggest that early and late phrenic fibers have different responses to chemical stimuli and to vagally mediated reflexes; late units do not discharge in postinspiratory period, whereas early fibers do; the PIIA is not affected in the same way by various chemical and vagal inputs; and early units that exhibit PIIA display tonic activity with hyperoxic hypocapnia.     

兔心迷走神经传出放电的活动特征

兔心迷走神经传出放电有三种类型:1.与后膈神经传出发放同步的节律性放电。这种节律性发放包含两个时相,第一时相大致与膈神经传出放电同时起止,第二时相在膈神经传出发放后期或发放终止时出现。2.持续性放电,出现在上述节律性放电的间歇期。3.偶然出现的高幅高频暴发放电。这种放电出现时,膈神经传出放电即受到明显的压抑。开放预先夹闭的颈总动脉使心迷走神经传出放电增强。窒息、静脉注射肾上腺素使心迷走神经传出放电增强,心率减慢;扩张肺、过度通气、吸入亚硝酸异戊酯使心迷走神经传出放电减少,心率增快。     

Effects of high-frequency oscillatory ventilation on vagal and phrenic nerve activities

This study was undertaken to define the mechanism for the respiratory inhibition observed during high-frequency oscillatory ventilation (HFOV). The effects of HFOV on the activities of single units in the vagus (Vna) and phrenic nerves (Pna) were examined in pentobarbital-anesthetized dogs. The animals were either ventilated by intermittent positive-pressure ventilation (IPPV) with and without positive end-expiratory pressure (PEEP), or by HFOV at a frequency of 25 Hz and pump displacement volume of 3 ml/kg. In 13 vagal units the Vna was much higher during HFOV than during IPPV or airway occlusion at a matched airway pressure. Ten units in the phrenic nerves were examined, and Pna (expressed as bursts/min) was attenuated by HFOV in all of them. In four of them, the effect of cooling the vagi to 8-10 degrees C on Pna was examined, and it was found that HFOV failed to alter the Pna. We conclude that 1) HFOV stimulates the pulmonary vagal afferent fibers continuously and to a degree greater than that due to static lung inflation and increased airway pressure and 2) the increased vagal activity during HFOV probably causes phrenic nerve activity inhibition.     

Observations on the hypoxic depression of sympathetic discharge in sinoaortic-denervated cats

The effect of graded isocapnic hypoxia on the mass activity of the cervical sympathetic trunk and of the phrenic nerve was studied in sinoaortic-denervated, pentobarbital-anaesthetized cats. Under control conditions (normoxia, normocapnia) sympathetic discharge showed (i) a burst of action potentials synchronous with the phrenic nerve burst, which was selectively abolished by procedures suppressing inspiratory neuron activity (inspiration synchronous sympathetic activity, ISSA); and (ii) a lower level of sympathetic activity during expiration (tonic sympathetic activity, TSA). The effects of graded hypoxia on these two components of the sympathetic discharge were different. ISSA showed depression only, which began at inspired PO2 (Pinsp O2) of 58 +/- 10 (mean +/- SEM) mmHg (1 mmHg = 133.3 Pa), became progressively more marked as Pinsp O2 decreased further, and was paralleled by depression of phrenic nerve activity. Both ISSA and phrenic nerve activity were suppressed at Pinsp O2 of 46 +/- 9 mmHg. TSA increased progressively with the lowering of Pinsp O2, beginning at a Pinsp O2 significantly lower than that at which ISSA depression began (50 +/- 13 mmHg, p less than 0.01). In the range of Pinsp O2 values intermediate between the thresholds for ISSA depression and for TSA increase, some animals showed a depression of TSA that reversed to an increase as Pinsp O2 decreased further. During brief (duration 1.5 +/- 0.2 min) episodes of cerebral ischemia produced by occlusion of the brachiocephalic and left subclavian artery, the two components of sympathetic discharge showed responses similar to those observed in hypoxia, namely depression of ISSA as well as depression and enhancement of TSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phrenic afferents and their role in inspiratory control

In anesthetized cats, with vagi cut and the spinal cord severed at the C8 level, phrenic motor and/or sensory discharge was recorded. Small afferent phrenic fibers were identified through their activation by lactic acid, hyperosmotic NaCl solution, or phenyl diguanide. They exhibited a spontaneous but irregular low-frequency discharge. Block of their conduction by procaine had no effect on eupneic motor phrenic activity. Large afferent phrenic fibers showed a spontaneous rhythmic discharge, and cold block (6 degrees C) of these fibers significantly prolonged the phrenic discharge time (Tphr) and total breath duration (TT) during eupnea. The stimulation of all afferent phrenic fibers lowered the impulse frequency of phrenic motoneurons (f impulses) and shortened both Tphr and TT. When the stimulation was performed during cold block all of the effects on phrenic output persisted, but changes in timing were less pronounced. Under procaine block, only the effects of phrenic nerve stimulation on Tphr persisted. These results suggest that both large and small afferent phrenic fibers control the inspiratory activity with a prominent role of small fibers on phrenic motoneuron impulse frequency.     

Augmentation of parasympathetic contraction in tracheal and bronchial airways by PGF2 alpha in situ

We studied the effect of exogenous prostaglandin F2 alpha (PGF2 alpha) on airway smooth muscle contraction caused by parasympathetic stimulation in 22 mongrel dogs in situ. Voltage (0-30 V, constant 20 Hz) and frequency-response (0-25 Hz, 25 V) curves were generated by stimulating the cut ends of both cervical vagus nerves. Airway response was measured isometrically as active tension (AT) in a segment of cervical trachea and as change in airway resistance (RL) and dynamic compliance (Cdyn) in bronchial airways. One hour after 5 mg/kg iv indomethacin, a cumulative frequency-response curve was generated in nine animals by electrical stimulation of the vagus nerves at 15-s intervals. Reproducibility was demonstrated by generating a second curve 7 min later. A third frequency-response curve was generated during active contraction of the airway caused by continuous intravenous infusion of 10 micrograms X kg-1 X min-1PPGF2 alpha. Additional frequency-response studies were generated 15 and 30 min after PGF2 alpha, when airway contractile response (delta RL = +2.8 +/- 0.65 cmH2O X 1(-1) X s; delta Cdyn = -0.0259 +/- 0.007 1/cmH2O) returned to base line. Substantial augmentation of AT, RL, and Cdyn responses was demonstrated in every animal studied (P less than 0.01 for all points greater than 8 Hz) 15 min after PGF2 alpha. At 30 min, response did not differ from initial base-line control. In four animals receiving sham infusion, all frequency-response curves were identical. We demonstrate that PGF2 alpha augments the response to vagus nerve stimulation in tracheal and bronchial airways. Augmentation does not depend on PGF2 alpha-induced active tone.     

Role of vagal afferents in the control of abdominal expiratory muscle activity in the dog.

We examined the contribution of afferent vagal A- and C-fibers on abdominal expiratory muscle activity (EMA). In seven spontaneously breathing supine dogs anesthetized with alpha-chloralose we recorded the electromyogram of the external oblique muscle at various vagal temperatures before and after the induction of a pneumothorax. When myelinated fibers were blocked selectively by cooling the vagus nerves to 7 degrees C, EMA decreased to 40% of control (EMA at 39 degrees C). With further cooling to 0 degrees C, removing afferent vagal C-fiber activity, EMA returned to 72% of control. On rewarming the vagus nerves to 39 degrees C, we then induced a pneumothorax (27 ml/kg) that eliminated the EMA in all the dogs studied. Cooling the vagus nerves to 7 degrees C, during the pneumothorax, produced a slight though not significant increase in EMA. However, further cooling of the vagus nerves to 0 degrees C caused the EMA to return vigorously to 116% of control. In three dogs, intravenous infusion of a constant incrementally increasing dose of capsaicin, a C-fiber stimulant, decreased EMA in proportion to the dose delivered. These results suggest that EMA is modulated by a balance between excitatory vagal A-fiber activity, most likely from slowly adapting pulmonary stretch receptors, and inhibitory C-fiber activity, most likely from lung C-fibers.     

Sacral anterior root stimulation and cryotechnique: A new option for selective urethral sphincter block and reversible deafferentation in the future?

A possible application of cryotechnique might be a selective block of nerve fiber activity during sacral anterior root stimulation to achieve selective block of urethral sphincter and reversible deafferentation. In 13 foxhounds, electrical stimulation of sacral anterior roots S2 was performed while the accompanying spinal nerves were simultaneously cooled down from +25 degrees C in a stepwise fashion until a block of urethral sphincter activity was observed. The effects of cold block on the urethral sphincter and bladder were monitored by urodynamic investigation. In 2 additional dogs sacral posterior roots S2 were cooled down to +3 degrees C while accompanying anterior and posterior roots were stimulated distal to the cryothermode. Compound action potentials (APs) were registered proximal to the cryothermode before, during and after cooling and recovery time of cold blocked nerves was evaluated. Complete cold block of the urethral sphincter during spinal nerve cooling was achieved in all cases. Block temperature averaged +12 degrees C. Detrusor pressure was a mean 5,2 cm water. Recovery time was on average 5 min. The cold block was always reversible. In both dogs of the second series the compound action potentials disappeared nearly completely at +3 degrees C. Three min after the end of the cooling period the appearance of the compound action potentials was back to normal. In this study, cryotechnique proved to be effective for selective and reversible block of nerve fibers during sacral anterior root stimulation. In functional electrical stimulation this technique may lead to an improvement of quality of life in para- or tetraplegic patients resulting in optimization of voiding, standing, walking and grasping and does so without the necessity of surgical dorsal root rhizotomy.     

Neuromuscular blocking in acutely tetanus intoxicated mice

The effects of tetanus toxin on neuromuscular transmission of mice in acute intoxication produced by intravenous injection of a large amount of the toxin were examined by (1) recording the phrenic nerve impulses, the electromyograms (EMGs) of the diaphragm and the electrocardiograms, and (2) the evoked EMGs of the gastrocnemius muscle in response to electrical stimulation of the sciatic nerve. The evoked EMGs of the gastrocnemius muscle were analyzed in terms of kinetic and tonic components by their different latencies. Just before death of animals, the EMGs of the diaphragm appeared with some delay relative to the corresponding phrenic discharges. Finally, the EMG of the diaphragm disappeared even in the presence of phrenic discharge, but cardiac electrical activities continued. The amplitudes of the evoked EMGs of the gastrocnemius muscle invariably became low before death, but the muscle action potential could be recorded by direct muscle stimulation for several minutes after death. The latencies of the evoked EMGs were constant until about the middle of the survival time when the latencies suddenly became prolonged. The longer latency was the same as that of the tonic action potentials. Thus, in acutely tetanus-intoxicated mice, neuromuscular transmission was blocked rapidly and the kinetic component of the muscle was blocked earlier than the tonic component.     

The effect of acute rise in intracranial pressure on the sympathetic cardiac, vertebral and phrenic nerve activities.

A transient rise of intracranial pressure in cats under chloralose-urethane anaesthesia increased the activity of the sympathetic vertebral nerve, cardiac nerve and in the first phase phrenic nerve. If the vagus nerves were intact this rise in sympathetic activity was associated with bradycardia. These effects developed with a delay, as a rule after abatement of the transient intracranial pressure rise. The authors suggest that Cushing's reaction is caused by medullary ischaemia and development of local metabolic acidosis activating simultaneously the sympathetic and parasympathetic neurons in the medulla oblongata.     

The initial heat production in garfish olfactory nerve fibres.

A study has been made of the temperature changes associated with the passage of a single impulse in the non-myelinated fibres of the garfish olfactory nerve: and the time course of these temperature changes has been compared with the time course of the electrical events during the action potential. As in other non-myelinated nerves studied the observed temperature changes result from a biphasic initial heat production consisting of a transient evolution of heat (the positive heat) followed by a rapid heat reabsorption (referred to as the negative heat). There is no evidence of any additional phases of initial heat production. At 0 degrees C the measured positive initial heat is 224 mucal/g impulse (937 muJ/g impulse); and the corresponding negative initial heat is 230 mucal/g impulse (962 muJ/g impulse). The residual initial heat is very small, being about -6 mucal/g impulse (-25 muJ/g impulse). In the range 0-10 degrees C there is no significant effect of temperature on the magnitude of either the positive or the negative phases of heat production. The experimental thermal records were analysed to determine the true time course of the temperature changes in the nerve undistorted by the recording system. The time course of the temperature changes does not fit with that of the transmembrane voltage change as represented by the monophasic compound action potential recorded externally from the same point on the nerve. A better fit is obtained if the temperature changes are compared with the square of the voltage change in accordance with the view that the heat derives almost wholly from free energy changes and entropy changes in the membrane capacity. The best fit is obtained if it is assumed that the membrane potential does not discharge to zero during the action potential but that at the peak of the action potential the charge (and hence the p.d.) across the membrane capacity retains about 24% of its resting value.     

PHOSPHOINOSITIDES AND OTHER PHOSPHOLIPIDS IN SYMPATHETIC GANGLIA AND NERVE TRUNKS OF RATS

Abstract— Paired vagus nerves, phrenic nerves or superior cervical sympathetic ganglia from adult white rats were incubated for 4 h at 37°C in a bicarbonate-buffered physiological solution containing glucose and ³²P₁. At the end of incubation triphosphoinositide (TPI) contained more ³²P than any other lipid in the vagus nerves and was second only to phosphatidylcholine (PC) in the phrenic nerves. In the sympathetic ganglia phosphatidylinositol (PI) contained more ³²P than did TPI, but both had less than PC. Conducted nerve impulses, initiated by electrical stimulation during the final 3 h of incubation, caused a highly significant increase in the [32P]-labelling of PI in ganglia (as previously reported) probably decreased the labelling of TPI in the vagus nerves, and decreased the labelling of phosphatidylethanolamine (PE) in the ganglia. Addition to the incubation medium of §- or γ-hexachlorocyclohexane (analogs of inositol) reversibly blocked transmission through the sympathetic ganglia at concentrations less than 0·1 mM. The §-isomer also blocked conduction along axons at similar concentrations; only the γ-isomer (lindane) exerted a selective effect on synaptic transmission. In the ganglia, the §-isomer increased the [³²P]-labelling of PI and diphosphoinositide (DPI) relative to that of PC. The γ-isomer did not affect the relative labelling of PI in the ganglia, whereas it decreased that of TPI, but only at relatively high concentrations. Thus, various affects of the hexachlorocyclohexanes were not explicable by assuming that they acted as analog inhibitors of inositol metabolism. In the ganglia, the hexachlorocyclohexanes reduced the effect of neuronal activity on the labelling of PI in proportion to the extent by which they blocked transmission. This metabolic effect was therefore presumed to be secondary to a ganglionic blocking action.     

Inhibitors of sensillar esterase reversibly block the responses of moth pheromone receptor cells

Three volatile alkyl-thio-trifluoro propanones inhibiting the esterase in olfactory sensilla of the silkmoths Antheraea polyphemus and A. pernyi were used to test the hypothesis that enzymatic pheromone degradation is responsible for the decline of the receptor potential after pheromone stimulation. Test stimuli were the pheromone components (E,Z)-6,11-hexadecadienyl acetate, a substrate for the sensillar esterase, and (E,Z)-6,11-hexadecadienal, not degraded by the esterase. Each compound acts on a separate type of receptor cell. In both receptor cell types the trifluoro propanones caused a partially reversible reduction of sensitivity as indicated by smaller receptor potential amplitudes and lower nerve impulse frequencies. Since application of the esterase inhibitors did not prolong the decline of the receptor potential of the acetate cell, the esterase is not responsible for the rapid pheromone deactivation. When the trifluoro propanones were applied after the pheromone at high concentrations, they rapidly inhibited (repolarized) both receptor cell types. Experiments with local application of trifluoro propanones revealed that the inhibitory effect spreads within seconds along the length of the sensillum. The inhibition of the electrophysiological responses might be due to an antagonistic action of the trifluoro propanones at the pheromone-binding sites, either at the receptor molecules or at the pheromone-binding protein. Accepted: 4 February 1998