Biomedical subjects

A Haji

Publications and source records attributed to A Haji.

At least 37 records · Page 2Linked to original sources

PubMed1996

Membrane potentials of respiratory neurones during dizocilpine-induced apneusis in adult cats.

1. In the vagotomized cat, blockade of NMDA receptors by dizocilpine (MK-801) produces an apneustic pattern of respiration characterized by a large increase in the duration of inspiration. 2. To identify dizocilpine-induced disfacilitations and disinhibitions in respiratory neurones generating the respiratory rhythm, membrane potential and input resistance of augmenting inspiratory (I; n = 11) and post-inspiratory (PI; n = 9) neurones were examined in the ventral respiratory group area, before and after administration of dizocilpine (0.1-0.3 mg kg-1 i.v.) in decerebrate, vagotomized, paralysed and artificially ventilated cats. 3. In I neurones, dizocilpine decreased the ramp depolarization and an 82% increase in input resistance was observed during inspiration. The inspiratory phase was prolonged, leading to a sustained level of depolarization during apneusis. The amplitude of stage 1 expiratory hyperpolarization decreased and its decay, which is normally slow, was faster. Throughout the remainder of expiration (stage 2) the membrane potential levelled off and the input resistance increased slightly (by 15%). 4. In PI neurones, dizocilpine depressed depolarization and suppressed firing in eight out of nine cells during the stage 1 expiratory phase. This was associated with a large (91%) increase of input resistance. The membrane potential switched quickly to stage 2 expiratory repolarization, during which a slight (19%) increase in input resistance occurred. 5. The hyperpolarization of PI neurones during early inspiration was reduced in amplitude by dizocilpine and input resistance was increased by 75% during inspiration, indicating that dizocilpine reduced the activity of the presynaptic inhibitory early-inspiratory (eI) neurones. 6. We conclude that NMDA receptor blockade in the respiratory network disfacilitates eI, I and PI neurones during their active phase. Decreased inhibitory processes during the inspiratory phase probably play a major role in the prolongation of inspiration.

Animals↗

PubMed1996

Protein kinase C pathways modulate respiratory pattern generation in the cat.

1. The significance of protein kinase C (PKC) in respiratory pattern generation was investigated in forty-three expiratory neurones of anaesthetized cats. 2. Intracellular injection of R-2,6-diamino-N-([1-(oxotridecyl)-2-piperidinyl]-methyl)-hexana mide dihydrochloride reversibly hyperpolarized twenty-six neurones. Respiratory drive potentials decreased to 92% of control, and action potential discharges were reduced. Neuronal input resistance (Rin) decreased during inspiration and increased during expiration. 3. Voltage clamp revealed that blockade of PKC induced an increase of inhibitory drive currents and a decrease of excitatory drive currents in sixteen neurones. The amplitude of respiratory drive currents was decreased to 91% of control. The slope of synaptic inward currents during postinspiration was reduced. 4. After blockade of K+ conductances by TEA, additional blockade of PKC caused a hyperpolarization during postinspiration and expiration, but depolarization during inspiration in fourteen neurones. The respiratory drive currents were reduced to 61% of control. Respiratory drive potentials decreased to 72% of control, leading to reduced spontaneous discharge. Rin was increased throughout the respiratory cycle. 5. Stimulus-evoked postsynaptic currents and potentials decreased after blockade of PKC with and without TEA. 6. The results indicate that PKC is endogenously active in expiratory neurones, modulating their excitability in three different ways: (a) it downregulates persistent K+ currents, (b) it upregulates Cl(-)-mediated inhibitory postsynaptic currents (IPSCs), and (c) it upregulates excitatory postsynaptic currents (EPSCs).

Animals↗

PubMed1996

Pharmacological properties of peripherally induced postsynaptic potentials in bulbar respiratory neurons of decerebrate cats.

Intracellular recordings of bulbar inspiratory and post-inspiratory neurons, combined with extracellular iontophoresis of antagonists of putative neurotransmitters, were performed in decerebrate cats. Inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of the superior laryngeal nerve or vagus nerve were depressed by bicuculline in all 22 neurons tested, but not modified by strychnine. The non-N-methyl-D-aspartate (NMDA) glutamate antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) decreased the neurally evoked excitatory postsynaptic potentials (EPSPs) in 23 out of 26 neurons tested, while the NMDA antagonist dizocilpine had no notable effect. The present results suggest that the peripherally induced IPSPs are mediated through gamma-aminobutyric acid (GABA)A receptors and the EPSPs through non-NMDA glutamate receptors in bulbar respiratory neurons.

Animals↗

PubMed1996

Effects on iontophoretically applied acetylcholine on membrane potential and synaptic activity of bulbar respiratory neurones in decerebrate cats.

Intracellular recordings were made from bulbar respiratory neurones of decerebrate cats, together with iontophoretic application of acetylcholine and its specific antagonists to assess cholinergic mechanisms involved in the central respiratory network in vivo. Of 126 respiratory-related neurones impaled in the ventral respiratory group, iontophoresis of acetylcholine produced depolarization in 67 cells (53%), hyperpolarization in 36 cells (29%), and no effect in the remaining 23 cells (18%). Depolarization occurred predominantly in laryngeal motoneurones (31/40) and bulbo-spinal neurones (4/5), while a comparable number of non-antidromically-activated respiratory neurones displayed either depolarization (33/81) or hyperpolarization (31/81). Acetylcholine had no significant effect on excitatory and inhibitory postsynaptic potentials in all types of neurones tested. Both depolarizing effects of acetylcholine were antagonized by co-iontophoresis of atropine, but not by hexamethonium. Input resistance was increased (7/9) or unchanged (2/9) in depolarized cells, whereas it was unaltered in all hyperpolarized cells tested (n = 6). The present results suggest that the distribution and functions of cholinergic muscarinic receptors are different for the laryngeal and bulbo-spinal types of respiratory neurones and the non-antidromically-activated respiratory neurones in the cat.

Acetylcholine↗

PubMed1995

Effects of sevoflurane on respiratory activities in the phrenic nerve of decerebrate cats.

Although the depressive effect of sevoflurane on ventilation has been reported, its potency and mode of action on the neural respiratory activity is still unclear. Therefore, the effects of sevoflurane on the phrenic nerve discharge and the respiratory timing were compared with those of halothane. The efferent activity of the phrenic nerve was recorded from decerebrate, un-anesthetized and artificially ventilated cats, and its power spectrum was calculated. The inspiratory and expiratory periods were measured. Sevoflurane and halothane of the doses of 0.5-1.5 MAC were inhaled for 15 min. With 0.5 MAC, sevoflurane decreased the total power and two dominant spectral components of the high-frequency oscillation and medium-frequency oscillation in the power spectrum. With the same MAC dose, halothane had a greater depressive effect in a normocapnic condition with the vagus nerves being intact. In a state of hypercapnia or after vagotomy, the effect of halothane was considerably attenuated whereas that of sevoflurane remained unaltered. Halothane increased the neural respiratory rate much more than sevoflurane in both normocapnic and hypercapnic states. Vagotomy significantly weakened the effect of halothane to increase the respiratory rate but did not modify the effect of sevoflurane. With 1.0-1.5 MAC, both anesthetics severely decreased the phrenic power spectra and the potency difference became indistinct. The present findings demonstrate that sevoflurane has a weaker depressive effect on the respiratory nerve discharge and a smaller effect on the neural respiratory rate than halothane when the effects of 0.5 MAC were compared.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1995

Differences in midazolam-induced breathing patterns in healthy volunteers.

Sex differences, and the influence of drug dosage and additional upper airway obstruction were studied in midazolam-induced breathing patterns and sedation in 30 healthy volunteers (8 males and 22 females). After administration of 0.1 mg.kg-1 midazolam (8 male and 8 female subjects), the rib cage (RC) motion increased in 6 males and the abdominal wall (ABD) motion and SaO2 decreased in all males. In contrast, the RC and ABD motions and SaO2 decreased in all females. Snoring and loss of consciousness occurred in 7 males and in 2 females. There were significant differences in the RC motion, SaO2, the incidence of snoring and the sedative state between male and female subjects. A bolus dose of 0.5 mg of flumazenil completely antagonized the sedative effect of midazolam and restored the breathing pattern, whereas it did not completely restore SaO2. A higher dose (0.2 mg.kg-1) of midazolam was administered to an additional 8 females. It caused a loss of consciousness in all subjects and increased the RC motion in only one subject. Partial obstruction of the nasal cavity was effected with cotton balls in the remaining 6 females who were sedated with 0.1 mg.kg-1 midazolam. An increase in the RC motion occurred similar to that observed in males. These findings suggest a difference in midazolam-induced sedation and breathing patterns between male and female subjects with midazolam administration on a mg.kg-1 basis.

Abdominal Muscles↗

PubMed1994

Increased feline cerebral blood flow induced by dehydroevodiamine hydrochloride from Evodia rutaecarpa.

Dehydroevodiamine hydrochloride (0.1-0.3 mg/kg iv), which was isolated from the leaves of Evodia rutaecarpa, increased the cerebral blood flow recorded from the surface of the supra-sylvian gyrus in anesthetized cats. This action reached a maximum 1-4 min after injection and continued for 10 min. However, the compound had negligible effects on other cardiorespiratory functions at the doses examined. These results suggest that the compound selectively increases cerebral blood flow.

Alkaloids↗

PubMed1993

Microiontophoresis of baclofen on membrane potential and input resistance in bulbar respiratory neurons in the cat.

Iontophoresis of baclofen produced hyperpolarization and a decrease in input resistance in 32 neurons and no effect in 24 neurons of the ventral respiratory group in cats. Iontophoresed phaclofen antagonized the effect of baclofen, but had negligible effects on periodic fluctuations in membrane potential and spike activity in these neurons. The hyperpolarizing effect of baclofen persisted after iontophoresis of tetrodotoxin, suggesting that baclofen acted directly at the postsynaptic gamma-aminobutyric acid (GABA)B receptors.

Action Potentials↗

PubMed1993

Mechanisms underlying post-inspiratory depolarization in post-inspiratory neurons of the cat.

The mechanism of the post-inspiratory depolarization in bulbar post-inspiratory neurons was investigated in decerebrate cats with a coaxial multibarrelled microelectrode technique. Iontophoresed tetrodotoxin eliminated a dominant part of the post-inspiratory depolarization and left a small depolarization to occur. This residual potential was increased with depolarization. When depolarization exceeded a potential of average -63 mV, there appeared a large bell-shaped depolarization that was suppressed by iontophoresed cadmium. These results suggest that the post-inspiratory depolarization in this neuron is formed by the cooperation between excitatory synaptic potentials and voltage-dependent Ca2+ currents.

Action Potentials↗

PubMed1993

Variations in membrane potential trajectory of post-inspiratory neurons in the ventrolateral medulla of the cat.

In decerebrate cats, intracellular recordings were made in 124 expiratory neurons displaying either a plateau-phase of depolarization during post-inspiration or a steadily decrementing depolarization throughout expiration. Both groups consisted of vagal motoneurons and non-antidromically activated neurons. Five neurons were antidromically activated by both vagal and spinal cord stimuli. The pattern in membrane potential was changed from one type to another either spontaneously or experimentally. The present results suggest that the variable appearance of the membrane potential trajectory does not represent the different functional category of bulbar post-inspiratory neurons.

Anesthesia↗

PubMed1993

Cellular effects of isoflurane on bulbar respiratory neurons in decerebrate cats.

Effects of isoflurane on the membrane potential trajectory and synaptic activity in bulbar respiratory neurons were investigated in decerebrate, vagotomized and artificially ventilated cats. A 2-min inhalation of 1.6% end-tidal concentration of isoflurane produced depolarization of the membrane in 10 out of 18 inspiratory, 8 out of 15 post-inspiratory and 5 out of 12 expiratory neurons and hyperpolarization in the rest of the population recorded in the ventral respiratory group. In both depolarized and hyperpolarized cells, periodically occurring excitatory and inhibitory synaptic waves were decreased, and input resistance was increased. Concomitantly, isoflurane reduced the excitatory and inhibitory postsynaptic potentials evoked by electrical stimulation of the vagus nerve, superior laryngeal nerve and cervical spinal cord. The effects of isoflurane on membrane potential and input resistance became negligible when excitatory and inhibitory synaptic potentials were suppressed by iontophoretically applied tetrodotoxin. The present results suggest that the respiratory neuronal responses induced by isoflurane are attributed mainly to the decrease of excitatory and inhibitory synaptic interactions in the bulbar respiratory network of neurons.

Action Potentials↗

PubMed1992

Effects of halothane on membrane potential and discharge activity in pairs of bulbar respiratory neurons of decerebrate cats.

In aiming to test the possibility of synaptic interactions, the effect of inhalation of halothane (2% for 90 sec) was studied on 45 out of 88 pairs of respiratory neurons, simultaneously recorded with intracellular and extracellular microelectrodes, in both sides of the ventral respiratory group of decerebrate cats. Halothane produced various effects on these respiratory neurons; namely, depolarization (n = 30) or hyperpolarization (n = 15) of intracellularly recorded neurons, an increase (n = 7) or decrease (n = 38) in the firing of extracellularly recorded neurons. However, with repeated application, the agent produced a consistent effect in a given cell. Spike-triggered averaging of synaptic noise, using spikes of non-antidromically-activated respiratory units, did not reveal any unitary postsynaptic potential but a symmetric synaptic wave of medium-frequency-oscillation (35-50 Hz) in 7 pairs. In addition, power spectral analysis of the membrane potential and spike-interval histogram of the paired neuron, displayed no correlated activity suggestive of synaptic interactions. For all the neuronal pairs examined, halothane produced random effects on their patterns of firing and synaptic waves. The present results suggest that halothane exerts a selective effect on each respiratory neuron and that the lack of a correlated response to application of halothane reflects the lack of synaptic interaction between pairs of bilaterally sampled neurons of the ventral respiratory group.

Action Potentials↗

PubMed1992

Evidence that glycine and GABA mediate postsynaptic inhibition of bulbar respiratory neurons in the cat.

Experiments were carried out on decerebrate cats to identify transsynaptic mediators of spontaneous postsynaptic inhibition of bulbar inspiratory and postinspiratory neurons. Somatic membrane potentials were recorded through the central micropipette of a coaxial multibarreled electrode. Blockers of type A gamma-aminobutyric acid (GABA-A) and glycine receptors were iontophoresed extracellularly from peripheral micropipettes surrounding the central pipette. Effective antagonism was demonstrated by iontophoresis of agonists with antagonists; application of strychnine antagonized the action of glycine but not GABA, and application of bicuculline antagonized the action of GABA but not glycine. In both types of neurons, iontophoresis of either antagonist depolarized the somatic membrane and increased input resistance throughout the respiratory cycle. Bicuculline preferentially depolarized the somatic membrane in both types of neurons during inactive phases. Strychnine increased the firing rate of inspiratory neurons during inspiration despite maintenance of somatic membrane potential at preiontophoresis levels. Tetrodotoxin reduced the effects of iontophoresed bicuculline and strychnine, suggesting that the action of the antagonists required presynaptic axonal conduction. The present results suggest that presynaptic release of both GABA and glycine contributes to tonic postsynaptic inhibition of bulbar respiratory neurons. GABA-A receptors appear to contribute to inhibition during inactive phases in inspiratory and postinspiratory neurons, whereas glycinergic mechanisms appear to contribute to inspiratory inhibition in inspiratory neurons.

Action Potentials↗

PubMed1991

Synaptic response of bulbar respiratory neurons to hypercapnic stimulation in peripherally chemodenervated cats.

Effects of hypercapnia on the membrane potential and synaptic activity of bulbar respiratory neurons were studied in decerebrate, vagotomized, glomectomized and artificially ventilated cats. Coaxial multibarrelled electrodes were used for intracellular recording and extracellular iontophoresis of drugs. Hypoventilation with oxygen-enriched air (hyperoxic hypercapnia) produced an increase of depolarization together with an increase of spiking during the active phase and an increase of hyperpolarization during the inactive phase of each respiratory cycle in the inspiratory, postinspiratory and expiratory neurons of the ventral respiratory group. Both depolarizing and hyperpolarizing effects were associated with a decrease in input resistance. Intracellular injection of Cl- reversed the polarity of the hyperpolarizing synaptic wave to depolarization during the inactive phase, and hypercapnia increased the depolarization at that phase. Iontophoresis of tetrodotoxin eliminated the CO2-induced changes in membrane potential and input resistance. In 20 out of 58 neurons examined, iontophoretically applied atropine partly or totally suppressed the depolarizing response to hypercapnia. For these neurons, iontophoresed acetylcholine produced a sustained depolarization that was antagonized by atropine, but not by hexamethonium. The present study shows that both depolarizing and hyperpolarizing responses of medullary respiratory neurons to hyperoxic hypercapnia are synaptically mediated. A muscarinic mechanism is involved in part of the respiratory neuronal excitation evoked by hypercapnia.

Acetylcholine↗

PubMed1990

Effects of acetaldehyde on contractile response to nerve stimulation in guinea-pig vas deferens.

Twitch contractions of the isolated guinea-pig vas deferens induced by sympathetic nerve stimulation were augmented by acetaldehyde (0.1-10 mM). With high concentrations (5-10 mM), acetaldehyde produced a biphasic response consisting of an initial brief depression and a subsequent potentiation of the contraction. The late effect was associated with repetitive contractions that were not prevented by tetrodotoxin. A low concentration of phentolamine (27 microM) increased and a high concentration (1.3 mM) suppressed the potentiating action of acetaldehyde. Acetaldehyde did not induce contractions in surgically sympathectomized vasa or vasa pretreated with reserpine. Acetaldehyde caused a dose-dependent increase in noradrenaline release into the bathing fluid. The study shows that acetaldehyde has a dual effect on sympathetic neuroeffector transmission, and that an increase in noradrenaline secretion appears to contribute to the late facilitatory effect in the isolated vas deferens.

Acetaldehyde↗

PubMed1990

Effects of acetaldehyde on electrical activity during neuroeffector transmission in guinea-pig vas deferens.

The effects of acetaldehyde on electrical activity during sympathetic neuroeffector transmission were studied in the guinea-pig vas deferens. Application of 1 mM acetaldehyde produced a slow depolarization of the smooth muscle membrane. The amplitudes of facilitated excitatory junction potentials (EJPs) evoked by nerve stimulation were slightly decreased. A higher concentration of acetaldehyde (5 mM) initially hyperpolarized and later depolarized the membrane. The decrease in EJP amplitudes was more pronounced during hyperpolarization. Acetaldehyde (5 mM) increased the frequency of the spontaneous EJPs and reduced their amplitudes, whereas action potentials in postganglionic nerves were unaffected. Acetaldehyde (1-5 mM) decreased the amplitudes of EJPs in vasa pretreated with reserpine but did not alter the resting membrane potentials. The decrease in the EJP amplitudes together with the hyperpolarization of the membrane could be responsible for the early inhibitory effect of acetaldehyde on neuroeffector transmission. The slow depolarization, which is presumably mediated by endogenous noradrenaline, may cause the late facilitatory effect.

Acetaldehyde↗

PubMed1990

Selective actions of anesthetic agents on membrane potential trajectory in bulbar respiratory neurons of cats.

The effects of two anesthetic agents, halothane and thiopental, on the membrane potential trajectory of respiratory-related neurons in the ventral respiratory group were investigated in decerebrate cats, of which the carotid sinus and vagal afferents were denervated. Infusion of halothane (2% for 90 s) depolarized the membrane in nearly half of the inspiratory (12/21), post-inspiratory (10/26) and expiratory (4/6) neurons and caused hyperpolarization in the rest of the population. Thiopental (2.5 mg/kg i.v.) produced depolarization in 11 inspiratory and 10 post-inspiratory neurons and hyperpolarization in 1 expiratory, 4 inspiratory and 7 post-inspiratory neurons. In both hyperpolarized and depolarized neurons, reduction of the respiratory membrane potential fluctuations and an increase of input resistance were commonly observed. Both drugs depressed spontaneous firing in most of the neurons studied. An increase of firing was observed in 9 out of 47 depolarized cells. These two contrasting effects on the membrane potential trajectory occurred similarly in the known groups of respiratory neurons, but the response of a given cell was consistent for the two anesthetic agents. The present results demonstrate that the anesthetic drugs exert various influences on the ventral respiratory group neuron population in maintaining the membrane potential trajectory and discharge activity. This may reflect a functional heterogeneity in the bulbar respiratory network of neurons.

Action Potentials↗

PubMed1990

Effects of ethanol on expiratory neuronal activities in decerebrated cats.

The effects of ethanol on two types of bulbar expiratory neurones, post-inspiratory (early expiratory) and expiratory (late expiratory) neurones, were studied in decerebrated, paralyzed and artificially ventilated cats. Intravenous injection of ethanol (300 mg/kg) depressed the efferent activity in the phrenic and recurrent laryngeal nerves which displayed the augmenting discharge during inspiration and the decrementing discharge during the early stage of expiration (stage I expiration). It reduced the duration of expiration, with a preferential effect on stage I expiration. Out of 22 medullary respiratory neurones consisting of 14 post-inspiratory and 8 expiratory neurones, 12 neurones were depolarized by ethanol and 10 neurones were hyperpolarized. In both cases, the respiratory fluctuations of membrane potential diminished and synaptic noises decreased. Input resistances of these neurones remained unchanged. Ethanol depressed the spike activity during stage I expiration of the post-inspiratory neurones. In expiratory neurones, a suppression of firing was greater in stage I expiration than in later stages of expiration. The present results demonstrate that ethanol reduces the expiratory period mainly through the depression of the post-inspiratory neuronal activity in the bulbar respiratory control mechanism.

Action Potentials↗