Biomedical subjects

Jean-François Perrier

Publications and source records attributed to Jean-François Perrier.

11 recordsLinked to original sources

PubMed2006

Improvement of donor myocardial function after treatment of autonomic storm during brain death.

BACKGROUND: In experimental brain death models, autonomic storm (AS) triggers severe myocardial dysfunction, which can be attenuated by pharmacologic treatment. The aim of this study was to determine the incidence of AS in a cohort of human organ donors and to evaluate the potential interest of AS treatment on myocardial function, cardiac harvesting and transplantation. METHODS: The cohort consisted of 152 patients. Among them, 46 patients were initially considered as potential cardiac donors (main criteria: age < 60 years, no history of cardiac disease). AS diagnosis included increased systolic arterial pressure > 200 mm Hg associated with tachycardia >140 beats/min. Heart acceptance criteria were associated creatine kinase (CK), troponin Ic, and left ventricle ejection fraction (LVEF) estimated by echocardiography and visual inspection. RESULTS: AS was observed in 29 patients (63%). Hypertension was treated in 12 patients (esmolol n = 6, urapidil n = 5, nicardipine). Cardiac harvesting was performed in 28 donors (61%). LVEFs were significantly higher after AS treatment (no AS: 55.4 +/- 13.4%, untreated AS: 49.0 +/- 18.8%, treated AS: 63.9+ +/- 10.3%, P = 0.049). AS treatment was found to be independently associated with LVEF in > 50% of the cases (P = 0.034). Treatment of AS or the lack of AS were associated with an increased probability of successful cardiac transplantation (OR = 8.8; 95% CI 2.1-38.3, P = 0.002). CONCLUSIONS: Treatment of hypertension during AS may attenuate brain death-induced myocardial dysfunction and increase the number of available cardiac grafts.

Adrenergic alpha-Antagonists↗

PubMed2006

Intrinsic properties shape the firing pattern of ventral horn interneurons from the spinal cord of the adult turtle.

Interneurons in the ventral horn of the spinal cord play a central role in motor control. In adult vertebrates, their intrinsic properties are poorly described because of the lack of in vitro preparations from the spinal cord of mature mammals. Taking advantage of the high resistance to anoxia in the adult turtle, we used a slice preparation from the spinal cord. We used the whole cell blind patch-clamp technique to record from ventral horn interneurons. We characterized their firing patterns in response to depolarizing current pulses and found that all the interneurons fired repetitively. They displayed bursting, adapting, delayed, accelerating, or oscillating firing patterns. By combining electrophysiological and pharmacological tests, we showed that interneurons expressed slow inward rectification, plateau potential, voltage-sensitive transient outward rectification, and low-threshold spikes. These results demonstrate a diversity of intrinsic properties that may enable a rich repertoire of activity patterns in the network of ventral horn interneurons.

Action Potentials↗

PubMed2005

Synaptic release of serotonin induced by stimulation of the raphe nucleus promotes plateau potentials in spinal motoneurons of the adult turtle.

Serotonin (5-HT) is a major modulator of the CNS. In motoneurons recorded in slices of the spinal cord, 5-HT promotes plateau potentials mediated by the activity of low-threshold L-type calcium channels (CaV1.3). However, no direct evidence has shown that 5-HT actually promotes plateau potentials under physiological conditions. Here, we investigate how release of 5-HT induced by activation of the raphe nucleus modulates intrinsic properties of spinal motoneurons. We developed an integrated preparation of the brainstem left in continuity with the cervical segments of the spinal cord from adult turtles. Electrical stimulation of the raphe nucleus increased the excitability of motoneurons by decreasing the amplitude of the afterhyperpolarization following action potentials and by promoting plateau potentials. Antagonists of 5-HT2 receptors applied in the vicinity of motoneurons inhibited the facilitation of plateaus. In a slice preparation in which glutamatergic, GABAergic, and glycinergic ionotropic synaptic transmission was blocked, stimulation of the dorsolateral funiculus facilitated a plateau potential by promoting a voltage-sensitive persistent inward current. This effect was inhibited by the addition of antagonists for 5-HT2 receptors. Our study suggests that CaV1.3 channels are regulated by 5-HT released from raphe spinal synaptic terminals via 5-HT2 receptors.

Action Potentials↗

PubMed2004

5-HT1A receptors modulate small-conductance Ca2+-activated K+ channels.

Small-conductance calcium-activated potassium channels (SK) are responsible for the medium afterhyperpolarisation (mAHP) following action potentials in neurons. Here we tested the ability of serotonin (5-HT) to modulate the activity of SK channels by coexpressing 5-HT1A receptors with different subtypes of SK channels (SK1, SK2, and SK3) in Xenopus laevis oocytes. SK channels were activated by intracellular injection of Cd2+. Subsequent activation of 5-HT1A receptors by 8-OH-DPAT always produced an inhibition of the SK current, showing the existence of a specific pathway between the receptor and the ion channel. To investigate the physiological relevance of this pathway, we characterized the mAHP present after action potentials in spinal motoneurons recorded in a slice preparation from the lumbar spinal cord of the adult turtle. By performing current and voltage clamp recordings, we showed that 8-OH-DPAT specifically inhibited the fraction of the AHP mediated by SK channels. We conclude that the activity of SK channels is modulated by activation of serotonergic receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2004

Recruitment of motor neuronal persistent inward currents shapes withdrawal reflexes in the frog.

The details of behaviour are determined by the interplay of synaptic connectivity within neuronal circuitry and the intrinsic membrane properties of individual neurones. One particularly dramatic intrinsic property displayed by neurones in many regions of the nervous system is membrane potential bistability, in which transient excitation of a neurone results in a persistent depolarization outlasting the initial excitation. Here we characterize the contribution of such intrinsic bistability, also referred to as plateau properties and mediated by persistent inward currents (PICs), in spinal motor neurones to the production of withdrawal behaviours in the frog. We performed experiments on the isolated frog spinal cord with attached hindlimb. This preparation allowed the simultaneous monitoring of muscle activations during motor behaviour and intracellular neuronal recordings. We found that PICs, following their potentiation by serotonin (5-HT), are recruited and contribute to the production of withdrawal behaviours. These properties conferred a voltage-dependent prolongation to the duration of motor neuronal activity. Consistent with this potentiation of motor neuronal PICs, 5-HT also increased the duration of evoked muscle activations. This behavioural potentiation, as well as the expression of PICs in individual neurones, was reduced following antagonism of L-type Ca(2+) channels. These results demonstrate that PICs in motor neurones can be recruited during the production of behaviour and play a role in specifying the temporal details of motor output.

Animals↗

PubMed2003

5-HT1A receptors increase excitability of spinal motoneurons by inhibiting a TASK-1-like K+ current in the adult turtle.

The modulatory effects of serotonin mediated by 5-HT1A receptors in adult spinal motoneurons were investigated by intracellular recordings in a slice preparation from the turtle. In current-clamp mode, activation of 5-HT1A receptors by 8-OH-DPAT led to depolarization and an increase in input resistance in most motoneurons but caused hyperpolarization and a decrease in input resistance in the remaining smaller fraction of cells. When slices were preincubated in medium containing the 5-HT1A receptor antagonist WAY-100635, 8-OH-DPAT had no effect. In voltage-clamp mode, with 1 mM CsCl in the bathing medium, 8-OH-DPAT consistently inhibited a leak current that was sensitive to extracellular acidification and anandamide, a TASK-1 channel blocker. In medium with a low pH, as in the presence of anandamide, 8-OH-DPAT had no effect. Our results show that activation of 5-HT1A receptors contributes to the excitatory effect of serotonin on spinal motoneurons by inhibition of a TASK-1 potassium channel leading to depolarization and increased input resistance.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2003

Subcellular distribution of L-type Ca2+ channels responsible for plateau potentials in motoneurons from the lumbar spinal cord of the turtle.

L-type calcium channels mediate the persistent inward current underlying plateau potentials in spinal motoneurons. Electrophysiological analysis shows that plateau potentials are generated by a persistent inward current mediated by low threshold L-type calcium channels located in the dendrites. As motoneurons express L-type calcium channels of the CaV1.2 and CaV1.3 subtypes, we have investigated the subcellular distribution of these channels using antibody labelling. The plateau generating a persistent inward current is modulated by the activation of metabotropic receptors. For this reason, we also examined the relationship between CaV1.2 and CaV1.3 subunits in motoneurons and presynaptic terminals labelled with antibodies against synapsin 1a. Motoneurons in the spinal cord of the adult turtle were identified as large neurons, immunopositive for choline acetyltransferase, located in the ventral horn. In these neurons, CaV1.2 subunits were present in the cell bodies and axons. Patches of CaV1.3 subunits were seen in association with the cell membrane of the somata and both the proximal and distal dendrites. Double labelling with an antibody against synapsin 1a showed that CaV1.3 subunits, but not CaV1.2 subunits, were always located at synaptic sites. The distribution of CaV1.2 and CaV1.3 strongly suggests that the persistent inward current underlying plateau potentials in spinal motoneurons is mediated by CaV1.3 and not by CaV1.2. Our findings also show that CaV1.3 may be located in the somatic and dendritic membrane adjacent to particular presynaptic terminals.

Animals↗

PubMed2003

5-HT2 receptors promote plateau potentials in turtle spinal motoneurons by facilitating an L-type calcium current.

The effects of serotonin (5-HT) on intrinsic properties of spinal motoneurons were investigated with intracellular recordings in a slice preparation from adult turtles. In 55% of the cells that were recorded, addition of 5-HT to the extracellular medium promoted plateau potentials as revealed by the response to depolarizing current pulses applied through the intracellular electrode. In the remaining 45% of cells, 5-HT had an inhibitory effect. However, when tested with an applied electric field that preferentially polarizes distal dendrites, 5-HT facilitated plateau potentials in 100% of the cells. Plateau potentials were also promoted by 5-HT focally applied on a dendrite by iontophoresis. Applied near the soma, 5-HT either promoted plateau potentials or inhibited spike generation. The latter effect was accompanied by a decrease in input resistance. Voltage-clamp recordings showed that the facilitation of plateau potentials mediated by L-type Ca(2+) channels was due to activation of 5-HT(2) receptors. These findings show that 5-HT regulates intrinsic properties of motoneurons in opposite ways: activation of 5-HT receptors in the soma region inhibits spike generation and plateau potentials, while activation of 5-HT(2) receptors in the dendrites and the soma region promotes spiking by facilitation of plateau potentials mediated by L-type Ca(2+) channels.

Action Potentials↗

PubMed2002

An M-like outward current regulates the excitability of spinal motoneurones in the adult turtle.

The excitatory action of muscarine on spinal motoneurones was investigated with intracellular recordings in a slice preparation from adult turtles. In these cells muscarine is known to facilitate a persistent inward current mediated by L-type Ca(2+) channels. When this effect was blocked by nifedipine, muscarine still increased the excitability. In voltage clamp, a slowly activating outward current, generated during depolarizing voltage commands and deactivating as a tail current on return to the holding voltage, was reduced by muscarine. This outward current was activated when the voltage was stepped to potentials positive to -60 mV, was voltage sensitive and had a deactivation time constant of approximately 80 ms. These findings are compatible with an M-current. This possibility was also supported by the finding that the current was reduced by XE-991 - a selective blocker of the KCNQ potassium channels underlying M-currents in other cell types. Our findings suggest that an M-like current, mediated by a KCNQ channel, contributes to the intrinsic response properties of motoneurones in the adult spinal cord by increasing adaptation of repetitive firing and decreasing the slope of the frequency-current relation.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2002

Mechanisms causing plateau potentials in spinal motoneurones.

Plateau potentials are generated by a voltage sensitive persistent inward current. In spinal motoneurones this current is predominantly mediated by influx of Ca2+ through L-type Ca2+ channels of the Ca(v)1.3 subtype. Depolarisation-induced facilitation of L-type Ca2+ channels is thought to be the mechanism for delayed activation (wind-up and warm-up) of the plateau potential and for the hysteresis in firing frequency and I-V relation during triangular depolarisation. L-type Ca2+ channels and plateau potentials in spinal motoneurones are facilitated by activation of metabotropic receptors for glutamate, acetylcholine, noradrenaline and serotonin and down regulated by activation of GABA(B) receptors. The facilitation has been shown to depend on activated calmodulin.

Animals↗

PubMed2002

Spinal plasticity mediated by postsynaptic L-type Ca2+ channels.

In the spinal cord, motoneurons and specific subgroups of interneurons express L-type Ca(2+) channels. As elsewhere, these dihydropyridine-sensitive channels mediate a slowly activating inward current in response to depolarisation and show little or no inactivation. The slow kinetics for activation and deactivation provide voltage-sensitive properties in a time range from hundreds of milliseconds to tens of seconds and lead to plateau potentials, bistability and wind-up in neurons in both sensory and motor networks. This slow dynamics is in part due to facilitation of L-type Ca(2+) channels by depolarisation. The voltage sensitivity of L-type Ca(2+) channels is also regulated by a range of metabotropic transmitter receptors. Up-regulation is mediated by receptors for glutamate, acetylcholine, noradrenaline and serotonin in motoneurons and by receptors for glutamate and substance P in plateau-generating dorsal horn interneurons. In both cell types, L-type Ca(2+) channels are down-regulated by activation of GABA(B) receptors. In this way, metabotropic regulation in cells expressing L-type Ca(2+) channels provides mechanisms for flexible adjustment of excitability and of the contribution of plateau currents to the intrinsic properties. This type of regulation also steers the magnitude and compartmental distribution of Ca(2+) influx during depolarisation, thus providing a signal for local synaptic plasticity.

Animals↗