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Biomedical subjects

A Haji

Publications and source records attributed to A Haji.

At least 19 recordsLinked to original sources
PubMed2006

Ryanodine receptor/Ca(2+) release mechanisms in rhythmically active respiratory neurons of cats in vivo.

The cytosolic Ca(2+) released from internal stores is important for distinctive cell functions. To assess the role of ryanodine/Ca(2+) releasing mechanisms in the rhythmic activity of respiratory neurons, effects of intracellular injection of ryanodine on the membrane potential trajectory of postinspiratory and augmenting inspiratory neurons were investigated in unanesthetized, decerebrate, paralyzed and artificially ventilated cats. Ryanodine injection hyperpolarized the membrane and decreased input resistance throughout the respiratory cycle in both types of respiratory neurons. Specifically, membrane repolarization during postinspiration was accelerated in postinspiratory neurons, and the large hyperpolarization at the onset of postinspiration was increased in augmenting inspiratory neurons. Spike-afterhyperpolarization consisting of a fast, early component and slow, late component increased in size after ryanodine, resulting in prolongation of inter-spike intervals and decrease of burst discharge. Intracellular injection of caffeine produced similar effects on these respiratory neurons, and Ruthenium Red, an antagonist of ryanodine receptors, had opposite effects. Immunoreactivity for ryanodine receptors was detected in all respiratory neurons labeled intracellularly with neurobiotin. These results demonstrate that ryanodine-sensitive Ca(2+) stores modulate the periodic membrane potential fluctuations and spike activity in respiratory neurons.

Animals↗
PubMed2005

An unusual case of traumatic petechiae.

We report a rare cause of traumatic petechiae without the full blown symptoms and signs of traumatic asphyxia. There were no complications encountered and there was spontaneous resolution.

Adult↗
PubMed2001

Glutamic acid decarboxylase-immunoreactivity of bulbar respiratory neurons identified by intracellular recording and labeling in rats.

To distinguish the GABAergic neuron in the ventral respiratory group (VRG) of rats, immunohistochemical staining of glutamic acid decarboxylase (GAD) was performed in neurons that had been individually identified by in vivo intracellular recording and labeling with neurobiotin. A total of five types of respiratory neurons were identified and labeled; augmenting inspiratory (aug-I, n=12), decrementing or early inspiratory (early-I, n=3), inspiration-expiration phase spanning or late inspiratory (late-I, n=3), decrementing expiratory or postinspiratory (PI, n=8), and augmenting or stage 2 expiratory (E2, n=3). In addition, expiration-inspiration phase-spanning or pre-inspiratory neurons (pre-I, n=2) were recorded, but not labeled. The membrane potential trajectory of each neuron type resembled that previously described in cat, suggesting a comparable neuronal organization between the two species. According to the axonal arborization, those labeled neurons were further classified as propriobulbar (6 aug-I, all early-I, all late-I, and 3 PI), bulbospinal (2 aug-I and all E2) and cranial-motor neurons (4 aug-I and 5 PI). GAD-immunoreactivity was consistently detected in the propriobulbar neurons, while it was not seen in cranial-motor and bulbospinal neurons. In addition, GAD-immunoreactive varicosities were found surrounding the somatic and dendritic surface of all labeled neurons. The present results illustrate that the propriobulbar types of early-I, aug-I, late-I and PI neurons are GABAergic inhibitory neurons and virtually all types of respiratory neurons receive GABAergic inputs in the rat's VRG.

Action Potentials↗
PubMed2001

Effects of a kappa-receptor agonist U-50488 on bulbar respiratory neurons and its antagonistic action against the mu receptor-induced respiratory depression in decerebrate cats.

The function of kappa receptor-mechanisms in bulbar respiratory network was investigated in decerebrate cats. Intravenous injection of U-50488 (0.3-3.0 mg/kg) dose-dependently decreased the phrenic nerve discharge and shortened inspiration and expiration. U-50488 caused hyperpolarization, and decreased input resistance and the action potential discharge in respiratory neurons. The effects of U-50488 were antagonized by nor-binaltorphimine. DAMGO (0.3 mg/kg, i.v.) decreased the phrenic discharge and prolonged inspiration and expiration. U-50488 partially reversed the respiratory depression induced by DAMGO. These results suggest that the activation of K receptors by itself depresses the central respiratory activity, while it opposes the mu receptor-mediated respiratory depression.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2000

Immunoreactivity for glutamic acid decarboxylase and N-methyl-D-aspartate receptors of intracellularly labeled respiratory neurons in the cat.

In adult cats, immunofluorescence images of glutamic acid decarboxylase (GAD) and N-methyl-D-aspartate (NMDA) receptors were achieved in the ventral respiratory group (VRG) neurons, which had been individually identified by in vivo intracellular recording and labeling with neurobiotin. Among augmenting inspiratory (aug-I), postinspiratory (post-I), and augmenting expiratory (aug-E) neurons labeled, GAD-immunoreactivity was demonstrated only in those neurons that were not antidromically activated (NAA) by stimulation of the vagus nerve and the C2-C3 spinal cord. Substantial immunoreactivity for NMDA receptors was presented in virtually all types of neurons, but lesser reactivity in aug-E bulbospinal neurons. These results suggest that the aug-I, post-I, and aug-E types of NAA neurons are gamma-aminobutyric acid (GABA)ergic and that NMDA receptors distribute in lesser degree in aug-E bulbospinal neurons than in other types of VRG neurons.

Animals↗
PubMed2000

Neuropharmacology of control of respiratory rhythm and pattern in mature mammals.

This review summarizes the current understanding of the neurotransmitters and neuromodulators that are involved, firstly, in respiratory rhythm and pattern generation, where glutamate plays an essential role in the excitatory mechanisms and glycine and gamma-aminobutyric acid mediate inhibitory postsynaptic effects, and secondly, in the transmission of input signals from the central and peripheral chemoreceptors and of motor outputs to respiratory motor neurons. Finally, neuronal mechanisms underlying respiratory modulations caused by respiratory depressants and excitants, such as general anesthetics, benzodiazepines, opioids, and cholinergic agents, are described.

Animals↗
PubMed2000

Contribution of NMDA receptors to activity of augmenting expiratory neurons in vagotomized cats.

To identify the NMDA receptor-mediated mechanism in augmenting expiratory (E2) neurons, the effects of systemic and local application of dizocilpine on spontaneous and evoked postsynaptic potentials (PSPs) were investigated in decerebrate and vagotomized cats. Intravenously applied dizocilpine reduced the inhibitory PSPs during inspiration and stage 1 expiration, but had little effect on the excitatory PSPs during stage 2 expiration. Iontophoresed dizocilpine caused a continuous hyperpolarization throughout the respiratory cycle. Dizocilpine had no effect on vagally evoked PSPs. These results suggest that the NMDA mechanisms are involved presynaptically in periodic postsynaptic inhibitions and postsynaptically in tonic excitation in E2 neurons.

Action Potentials↗
PubMed1999

Calcium currents in respiratory neurons of the cat in vivo.

Under in vivo conditions, periodic burst discharges of medullary respiratory neurons of mature cat typically start with a rebound depolarization when inhibition through antagonistic neurons stops. This rebound can be blocked by ionophoretically applied extracellular Cd2+. A similar Cd(2+)-sensitive rebound depolarization is triggered by hyperpolarizing current pulses even in the presence of extracellular tetrodotoxin (TTX) and tetraethylammonium (TEA). In current-clamp mode, the current/voltage (I/V) curves rectify outwardly at positive voltages, and this rectification is blocked by Cd2+. Intracellular injection of the L-type Ca(2+)-channel blocker methoxy-verapamil changes the spontaneous activity patterns of neurons. In those neurons that typically show augmenting patterns, the membrane depolarization is slowed down, while in those neurons that have a declining pattern, voltage changes become augmenting. Voltage-clamp measurements reveal a transient, low-voltage-activated T-type Ca2+ current. The current is deinactivated at -100 mV and almost completely inactivated at -60 mV. Depolarizing voltage commands starting from more positive holding potentials evoke sustained Ca2+ currents that reach a maximum at 0 mV. The sustained L-type Ca2+ currents are completely blocked by extracellular Cd2+. We conclude that low- and high-voltage-activated Ca2+ currents are expressed in all types of respiratory neurons and play an essential role in rhythm generation and pattern formation in adult cats in vivo.

Animals↗
PubMed1999

Related changes in sympathetic activity, cerebral blood flow and intracranial pressure, and effect of an alpha-blocker in experimental subarachnoid haemorrhage.

We investigated the changes in sympathetic nerve activity (SNA) and cerebral blood flow (CBF) with or without increase in intracranial pressure (ICP) in the acute stage of experimental subarachnoid haemorrhage (SAH). ICP was increased or controlled by rapid or slow injection of blood and saline, and the effect of an alpha-blocker, phentolamine, was also investigated in each condition. Following marked increase in ICP induced by rapid injection of blood or saline, increase in intracranial and general SNA and decrease in CBF were observed. Both changes were significantly decreased in magnitude by prior administration of phentolamine. When increase in ICP was not induced, by slow injection of blood, both SNA and CBF decreased, and these changes were alleviated by phentolamine. However, when increase in ICP was not induced by saline, neither SNA nor CBF significantly changed. These findings suggest that marked increase in ICP is the primary cause of the pathological changes occurring immediately after SAH, and that the decrease in CBF in mild SAH without increase in ICP is caused by blood itself. Administration of an alpha-blocker may be effective in improving the abnormal sympathetic nervous system induced by marked increase in ICP.

Adrenergic alpha-Antagonists↗
PubMed1999

GABA(A) receptor-mediated inspiratory termination evoked by vagal stimulation in decerebrate cats.

To identify the GABAergic inhibitory mechanisms involved in inspiratory termination or off-switching (IOS), the effects of a specific enhancer of GABA(A) receptors, midazolam, and an antagonist, bicuculline, on vagally evoked inspiratory inhibitions and IOS were investigated in decerebrate cats. Stimulation of vagal afferents at late inspiration provoked either reversible inspiratory inhibition or IOS, depending on the stimulus intensity. Each response occurred at a constant latency (phase 1). The reversible response was triphasic, consisting of an early (phase 2) inhibition, a brief (phase 3) excitation and a late (phase 4) inhibition in the phrenic neurogram, and early (phase 2) IPSPs, brief (phase 3) EPSPs and late (phase 4) IPSPs in bulbar inspiratory (I) neurones. With an increasing stimulus intensity, phase 4 inhibitions were increased in amplitude and duration, leading to IOS. Midazolam (0.1 mg/kg i.v.) increased more selectively phase 4 IPSPs than phase 2 IPSPs in I neurones, and decreased the threshold for evoking IOS by producing an earlier and larger phase 4 IPSPs. Bicuculline (1.0 mg/kg i.v.) had an opposite effect. These results suggest that the late inhibitory response evoked by vagal stimulation in the I neuronal pool organizes an initial phase of IOS which is mediated by GABA(A) receptors.

Animals↗
PubMed1999

Synaptic interactions between respiratory neurons during inspiratory on-switching evoked by vagal stimulation in decerebrate cats.

To elucidate neuronal mechanisms underlying phase-switching from expiration to inspiration, or inspiratory on-switching (IonS), postsynaptic potentials (PSPs) of bulbar respiratory neurons together with phrenic nerve discharges were recorded during IonS evoked by vagal stimulation in decerebrate and vagotomized cats. A single shock stimulation of the vagus nerve applied at late-expiration developed an inspiratory discharge in the phrenic neurogram after a latency of 79+/-11 ms (n = 11). Preceding this evoked inspiratory discharge, a triphasic response was induced, consisting of an early silence (phase 1 silence), a transient burst discharge (phase 2 discharge) and a late pause (phase 3 pause). During phase 1 silence, IPSPs occurred in augmenting inspiratory (aug-I) and expiratory (E2) neurons, and EPSPs in postinspiratory (PI) neurons. During phase 2 discharge, EPSPs arose in aug-I neurons and IPSPs in PI and E2 neurons. These initial biphasic PSPs were comparable with those during inspiratory off-switching evoked by the same stimulation applied at late-inspiration. In both on- and off-switching, phase-transition in respiratory neuronal activities started to arise concomitantly with the phrenic phase 3 pause. These results suggest that vagal inputs initially produce a non-specific, biphasic response in bulbar respiratory neurons, which consecutively activates a more specific process connected to IonS.

Animals↗
PubMed1998

Synaptic potentials in respiratory neurones during evoked phase switching after NMDA receptor blockade in the cat.

1. Blockade of NMDA receptors by dizocilpine impairs the inspiratory off-switch (IOS) of central origin but not the IOS evoked by stimulation of sensory afferents. To investigate whether this difference was due to the effects of different patterns of synaptic interactions on respiratory neurones, we stimulated electrically the superior laryngeal nerve (SLN) or vagus nerve in decerebrate cats before and after i.v. administration of dizocilpine, whilst recording intracellularly. 2. Phrenic nerve responses to ipsilateral SLN or vagal stimulation were: at mid-inspiration, a transient inhibition often followed by a brief burst of activity; at late inspiration, an IOS; and at mid-expiration, a late burst of activity. 3. In all neurones (n = 16), SLN stimulation at mid-inspiration evoked an early EPSP during phase 1 (latency to the arrest of phrenic nerve activity), followed by an IPSP in inspiratory (I) neurones (n = 8) and by a wave of EPSPs in post-inspiratory (PI) neurones (n = 8) during phase 2 (inhibition of phrenic activity). An EPSP in I neurones and an IPSP in PI neurones occurred during phase 3 (brief phrenic burst) following phase 2. 4. Evoked IOS was associated with a fast (phase 1) activation of PI neurones, whereas during spontaneous IOS, a progressive (30-50 ms) depolarization of PI neurones preceded the arrest of phrenic activity. 5. Phase 3 PSPs were similar to those occurring during the burst of activity seen at the start of spontaneous inspiration. 6. Dizocilpine did not suppress the evoked phrenic inhibition and the late burst of activity. The shapes and timing of the evoked PSPs and the changes in membrane potential in I and PI neurones during the phase transition were not altered. 7. We hypothesize that afferent sensory pathways not requiring NMDA receptors (1) terminate inspiration through a premature activation of PI neurones, and (2) evoke a late burst of phrenic activity which might be the first stage of the inspiratory on-switch.

Animals↗
PubMed1998

NMDA receptor-mediated inspiratory off-switching in pneumotaxic-disconnected cats.

The pneumotaxic center is thought to govern inspiratory off-switching (IOS), and blockade of N-methyl-D-aspartate (NMDA) receptors by dizocilpine impairs IOS causing apneusis. The present study is to examine whether the NMDA receptor-mediated IOS mechanism functions in the medullary respiratory network after disconnecting the pneumotaxic center. In decerebrate and vagotomized cats, the nucleus parabrachialis medialis (NPBM) and vagus nerves were stimulated to evoke IOS and a dorsal pontine transection was performed while the central respiratory activity was recorded in phrenic neurogram. The transection eliminated the NPBM-stimulated IOS but not the vagally evoked IOS, and developed two types of respiration; eupnea in 12 and apneusis in six out of 18 cats. Apneustic respiration was not changed into eupneic one by changing the end-tidal CO2 level. In animals displaying eupnea after the transection, dizocilpine (0.3 mg/kg i.v.) produced apneusis, characterized by a prolonged inspiration, a shortened stage 1 expiration and an unchanged stage 2 expiration. Dizocilpine caused no further change in the apneustic pattern induced by the transection. The present results suggest that the medullary respiratory network is able to generate a eupneic respiration after disconnecting the pontine pneumotaxic center, and the NMDA mechanism plays an important role in the medullary respiratory network.

Age Factors↗
PubMed1997

Intracellular signal pathways controlling respiratory neurons.

Medullary respiratory neurons are influenced by a variety of neuromodulators, but there is a lack of information about the specific intracellular signal pathways involved. In this report we describe the modulatory effects of the cyclic adenosine-triphosphate (cAMP)-dependent protein kinase and of protein kinase C pathways on voltage- and ligand-controlled ionic conductances and demonstrate their functional significance in regulating the excitability of medullary respiratory neurons of the vivo cat. Evidence is presented that PKA and PKC pathways are persistently activated. PKA regulates current flow through persistently activated and GABAB receptor-controlled potassium channels as well as GABAA receptor-controlled chloride channels. PKC also depresses persistent potassium currents but it potentiates excitatory and inhibitory synaptic currents. The clinical significance of these intracellular signal pathways is demonstrated in a case of a child suffering from apneustic breathing, who was successfully treated with a 5HT-1A receptor agonist.

Animals↗
PubMed1997

Effects of isoflurane on brain stem blood flow and renal sympathetic nerve activity during induced hypotension.

Effects of isoflurane on arterial blood pressure, regional blood flow in the brain stem, and renal sympathetic nerve activity were compared with those during vasodilator-induced hypotension using decerebrate unanesthetized cats. Either prostaglandin E1 (PGE1) or trinitroglycerin (TNG) was used to decrease the mean arterial pressure 30% below the control level. The effects of isoflurane (0.5 MAC for 15 min) were examined in the following three conditions: (1) during PGE1-induced hypotension; (2) during TNG-induced hypotension, and (3) without either vasodilator. Isoflurane decreased the brain stem blood flow in parallel with a systemic blood pressure fall. Electrical activity of the renal sympathetic nerve consisted of a high-amplitude phasic and a low-amplitude tonic discharge. Isoflurane decreased the phasic activity and increased the tonic activity. Although the two vasodilators had a similar effect on systemic blood pressure and renal sympathetic discharge, TNG decreased the brain stem blood flow to a lesser extent than PGE1. However, the effects of isoflurane on all parameters were statistically identical in the three conditions not treated and pretreated with either vasodilator. Also, the blood concentrations of isoflurane did not differ among the three conditions. The present study demonstrates that isoflurane produces similar effects on systemic blood pressure, regional cerebral blood flow and sympathetic efferent discharge during vasodilator-induced hypotension and without any vasodilator.

Alprostadil↗
PubMed1997

A modified coaxial compound micropipette for extracellular iontophoresis and intracellular recording: fabrication, performance and theory.

Investigation of the identity and modes of action of neurotransmitters in the mammalian central nervous system can be facilitated by simultaneous intracellular recording of membrane potential and extracellular iontophoresis of agonists and antagonists. We describe here techniques for conveniently constructing a compound microelectrode, originally described by Sonnhof (Pflugers Arch 341, 351-358, 1973), suitable for such studies. The Sonnhof electrode consists of two components, a centraxial micropipette for recording membrane potential surrounded by a cylindrical array of 6 pipettes for iontophoresis. The cylindrical array tapers coaxially and terminates in 6 contiguous, crescent-shaped orifices surrounding the terminal portion of the central pipette, 25 - 50 microm from the tip. Pipettes were constructed from borosilicate glass tubing of 1-mm wall thickness having a 10-mm or 16-mm outer diameter. The resistances, flux and transport numbers for iontophoresis of glycine were measured for pipettes constructed from both sizes of glass. Flux increased with increasing levels of current, and transport number decreased with increasing micropipette resistance. A spherical diffusion model points out the steep dependence of steady state concentration on diffusional distance, stressing the importance of diminishing the distance between the iontophoresis source and the recording site. This is particularly true when brief pulses of current are used.

Animals↗