Tonic Component Research Articles

Antispasmodic effects of a new kaurene diterpene isolated from Croton argyrophylloides on rat airway smooth muscle

The effects of rel-(1S,4aS,7S,8aS)-7-(1-vinyl)-tetradecahydro-1,4a-dimethylphenanthrene-7,8a-carbolactone-1-carboxylic acid (TCCA), a new ent-kaurene diterpene isolated from Croton argyrophylloides, on rat tracheal preparations were investigated. Tracheae were removed and cut into two-cartilage segments that were mounted in organ baths containing Tyrode's solution. TCCA reduced the contractions induced by electrical field stimulation, relaxed K(+)-induced contractions, and inhibited both phasic and tonic components of the K(+)- and ACh-induced contractions. TCCA reduced the serotonin-induced contraction, abolished that evoked by K(+) in the presence of epinephrine, and also reduced the ACh-induced contractions under Ca(2+)-free conditions. TCCA blocked contractions that depend on divalent cation inflow through voltage-operated Ca(2+) channels (VOCCs) and receptor-operated Ca(2+) channels (ROCCs), but had greater potency to block VOCC- than ROCC-dependent contractions or contractions induced by ACh in Ca(2+)-free conditions. TCCA relaxed the phorbol 12,13 dibutyrate (1 µm) induced contraction, but with slight potency. TCCA induces an antispasmodic effect through several mechanisms including blockade of either VOCCs (with greater potency) or ROCCs, blockade of IP(3)-induced Ca(2+) release from sarcoplasmic reticulum (with intermediate potency) and reduction of the sensitivity of contractile proteins to Ca(2+).

Changes of cytosolic calcium and contractility of young rat vas deferens by acute treatment with amphetamine, fluoxetine or sibutramine

Previous studies conducted in our laboratory indicated that administration of amphetamine, fluoxetine or sibutramine affects the sympathetic nervous system of the rat vas deferens. Therefore, our goal was to verify the role of calcium in vasa deferentia from young rats pretreated with a single dose of these drugs. Young 40-day-old male Wistar rats were pretreated with amphetamine 3mg/kg, fluoxetine 10mg/kg or sibutramine 6mg/kg for 4h before the experiments. CaCl2 (10mM) was used to induce contraction through time–effect curves in calcium-free solution to measure phasic and tonic components. We also evaluated the calcium-induced fluorescence of vas deferens cut into thin slices. In rats pretreated with amphetamine, we found an increase of the tonic contraction component which was reduced by verapamil. The phasic and tonic responses were increased in the group treated with fluoxetine, but only the tonic response was more sensitive to the antagonism by verapamil. The group treated with sibutramine showed an increase of phasic response whereas the tonic component was decreased. In this group an increase of the affinity for verapamil antagonism was found. In the calcium fluorescence study it was observed that the group treated with amphetamine, fluoxetine or sibutramine showed higher basal Ca2+ fluorescence after stimulus with KCl (70mM), noradrenaline (10−4M) or acetylcholine (10−4M). In all pretreated groups the calcium fluorescence was diminished by nifedipine 10−7M. Therefore, the pretreatment with amphetamine, fluoxetine or sibutramine seems to affect the calcium contractility and homeostasis in young rat vas deferens.

Faster, Deeper, Better: The Impact of Sniffing Modulation on Bulbar Olfactory Processing

A key feature of mammalian olfactory perception is that sensory input is intimately related to respiration. Different authors have considered respiratory dynamics not only as a simple vector for odor molecules but also as an integral part of olfactory perception. Thus, rats adapt their sniffing strategy, both in frequency and flow rate, when performing odor-related tasks. The question of how frequency and flow rate jointly impact the spatio-temporal representation of odor in the olfactory bulb (OB) has not yet been answered. In the present paper, we addressed this question using a simulated nasal airflow protocol on anesthetized rats combined with voltage-sensitive dye imaging (VSDi) of odor-evoked OB glomerular maps. Glomerular responses displayed a tonic component during odor stimulation with a superimposed phasic component phase-locked to the sampling pattern. We showed that a high sniffing frequency (10 Hz) retained the ability to shape OB activity and that the tonic and phasic components of the VSDi responses were dependent on flow rate and inspiration volume, respectively. Both sniffing parameters jointly affected OB responses to odor such that the reduced activity level induced by a frequency increase was compensated by an increased flow rate.

Glutamate modulates the firing rate in oculomotor nucleus motoneurons as a function of the recruitment threshold current

Studies in alert preparations have demonstrated that ocular motoneurons exhibit a phasic–tonic firing rate related to eye velocity and position, respectively. The slopes of these relationships are higher in motoneurons with higher recruitment threshold and have been proposed to depend upon synaptic input. To investigate this hypothesis, motoneurons of the rat oculomotor nucleus were recorded in a brain slice preparation in control conditions and during glutamate (5 μm) application to the bath. Glutamate did not affect membrane potential or input resistance, but produced a decrease in rheobase and depolarization voltage as a function of the current needed for generating a maintained repetitive discharge (recruitment threshold current). In addition, glutamate compressed the range of recruitment threshold current (0.1–0.4 nA) as compared to the control (0.15–0.7 nA). Glutamate exposed motoneurons showed an increase in the tonic frequency gain and the peak frequency. Such increments depended on the recruitment threshold current and the last recruited motoneurons almost doubled the tonic frequency gain (35.2 vs. 57.9 spikes s(−1) nA(−1)) and the peak frequency (52.4 vs. 102.6 spikes s(−1)). Finally, glutamate increased the spike frequency adaptation due to a significant increase in the phasic firing component as compared to the tonic one. In conclusion, glutamate modulates tonic and phasic discharge properties as a function of the recruitment threshold current and, presumably, motoneuron size. These findings contribute to understand the link between cellular functions and motoneuron discharge during oculomotor behaviour.

1011 EFFECT OF MELANOTAN II, A MELANOCORTIN AGONIST, ON SEXUAL BEHAVIOR SUPPRESSED BY PSYCHOLOGICAL STRESS IN MALE RATS

acetylcholine (Ach, 10 to 3 x 10M) were added with various concentrations into organ bath to induce isometric contraction of the isolated rat seminal vesicles. The dose response curve of the isolated rat seminal vesicles reacting to PE and Ach, the inhibitory dose response curve to the different adrenergic antagonists (prazosin for 1, WB-4101 for 1a, Chloroethylclonidine CEC for 1b), muscarinic antagonists (atropine for M, pirenzepine for M1, methoctramine for M2, and 4-DAMP for M3) and cross-over reaction were recorded. The twitch pattern of SVSM contraction was analyzed according to its phasic and tonic components. RESULTS: PE and Ach could both achieve good contraction of rat seminal vesicle. The IC50 of prazosin and WB-4101 were far greater than that of CEC. The IC50 of 4-DAMP was very close to atropine. PE and Ach could cause different patterns of SVSM twitch. PE induced SVSM contraction had more tonic components, but Ach induced SVSM contraction had more phasic components. CONCLUSIONS: The predominant subtypes of adrenergic and cholinergic receptors on rat seminal vesicle are £ 1a and M3 respectively. Different drugs also cause different pattern of SVSM twitch. In our speculation, sympathetic effect is more dominant during emission stage to squeeze seminal fluid out; however, parasympathetic effect is more dominant during ejection stage and provides an anti-reflux effect on ejaculatory duct. Further studies for realizing physiology of ejaculation are worthy.

Phasic GABAA‐receptor activation is required to suppress epileptiform activity in the CA3 region of the immature rat hippocampus

Despite the consistent observation that γ-aminobutyric acid A (GABA(A) ) receptors mediate excitatory responses at perinatal stages, the role of the GABAergic system in the generation of neonatal epileptiform activity remains controversial. Therefore, we analyzed whether tonic and phasic GABAergic transmission had differential effects on neuronal excitability during early development. We performed whole cell patch-clamp and field potential recordings in the CA3 region of hippocampal slices from immature (postnatal day 4-7) rats to analyze the effect of specific antagonists and modulators of tonic and phasic GABAergic components on neuronal excitability. The GABAergic antagonists gabazine (3 μm) and picrotoxin (100 μm) induced epileptiform discharges, whereas activation of GABA(A) receptors attenuated epileptiform discharges. Under low-Mg(2+) conditions, 100 nm gabazine and 1 μm picrotoxin were sufficient to provoke epileptiform activity in 63.2% (n = 19) and 53.8% (n = 26) of the slices, respectively. Whole-cell patch-clamp experiments revealed that these concentrations significantly reduced the amplitude of phasic GABAergic postsynaptic currents but had no effect on tonic currents. In contrast, 1-μm 4,5,6,7-tetrahydroisoxaz-olo[5,4-c]-pyridin-3-ol (THIP) induced a tonic current of -12 ± 2.5 pA (n = 6) and provoked epileptiform discharges in 57% (n = 21) of the slices. We conclude from these results that in the early postnatal rat hippocampus a constant phasic synaptic activity is required to control excitability and prevent epileptiform activity, whereas tonic GABAergic currents can mediate excitatory responses. Pharmacologic intervention at comparable human developmental stages should consider these ambivalent GABAergic actions.

0842 Episodic loss of consciousness in the toilet

A 21-year-old student presented with events of loss of consciousness whilst passing urine since the age of nine. After voiding a small quantity of urine, she would lose awareness and...

Bestrophin1 Channels are Insensitive to Ethanol and Do not Mediate Tonic GABAergic Currents in Cerebellar Granule Cells

The granule cell layer of the cerebellum functions in spatio-temporal encoding of information. Granule cells (GCs) are tonically inhibited by spillover of GABA released from Golgi cells and this tonic inhibition is facilitated by acute ethanol. Recently, it was demonstrated that a specialized Ca2+-activated anion-channel, bestrophin1 (Best1), found on glial cells, can release GABA that contributes up to 50–75% of the tonic GABAergic current. However, it is unknown if ethanol has any actions on Best1 function. Using whole-cell electrophysiology, we found that recombinant Best1 channels expressed in HEK-293 cells were insensitive to 40 and 80 mM ethanol. We attempted to measure the Best1-mediated component of the tonic current in slices using 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). We confirmed that this agent blocks recombinant Best1 channels. Unexpectedly, we found that NPPB significantly potentiated the tonic current and the area and decay of GABAA-mediated spontaneous inhibitory post-synaptic currents (IPSCs) in GCs in rodent slices under two different recording conditions. To better isolate the Best1-dependent tonic current component, we blocked the Golgi cell component of the tonic current with tetrodotoxin and found that NPPB similarly and significantly potentiated the tonic current amplitude and decay time of miniature IPSCs. Two other Cl−-channel blockers were also tested: 4′-diisothiocyanatostilbene-2,2′-disulfonic acid disodium salt hydrate (DIDS) showed no effect on GABAergic transmission, while niflumic acid (NFA) significantly suppressed the tonic current noise, as well as the mIPSC frequency, amplitude, and area. These data suggest that acute ethanol exposure does not modulate Best1 channels and these findings serve to challenge recent data indicating that these channels participate in the generation of tonic GABAergic currents in cerebellar GCs.

KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy

KCNQ2 and KCNQ3 mutations are known to be responsible for benign familial neonatal seizures (BFNS). A few reports on patients with a KCNQ2 mutation with a more severe outcome exist, but a definite relationship has not been established. In this study we investigated whether KCNQ2/3 mutations are a frequent cause of epileptic encephalopathies with an early onset and whether a recognizable phenotype exists. We analyzed 80 patients with unexplained neonatal or early-infantile seizures and associated psychomotor retardation for KCNQ2 and KCNQ3 mutations. Clinical and imaging data were reviewed in detail. We found 7 different heterozygous KCNQ2 mutations in 8 patients (8/80; 10%); 6 mutations arose de novo. One parent with a milder phenotype was mosaic for the mutation. No KCNQ3 mutations were found. The 8 patients had onset of intractable seizures in the first week of life with a prominent tonic component. Seizures generally resolved by age 3 years but the children had profound, or less frequently severe, intellectual disability with motor impairment. Electroencephalography (EEG) at onset showed a burst-suppression pattern or multifocal epileptiform activity. Early magnetic resonance imaging (MRI) of the brain showed characteristic hyperintensities in the basal ganglia and thalamus that later resolved. KCNQ2 mutations are found in a substantial proportion of patients with a neonatal epileptic encephalopathy with a potentially recognizable electroclinical and radiological phenotype. This suggests that KCNQ2 screening should be included in the diagnostic workup of refractory neonatal seizures of unknown origin.

Relaxant effect of trans-resveratrol on isolated porcine coronary arteries.

Recent studies provided evidence that trans-resveratrol (3,4',5-trihydroxystilbene, found in high concentrations in some red wines, may possibly decrease the risk of coronary heart disease mortality. The aim of this study, performed with large epicardial porcine coronary arteries (PCA) strips, was to investigate the relaxant effect of trans-resveratrol on these main conductance vessels, which have been described to be pathologically prone for vasospastic contractions. The data show that the tonic component of the biphasic contractions induced by histamine, as well as the contractions induced by F- ions (10 mmol/l), which activate G proteins downstream of the receptors, could dose-dependently be inhibited by trans-resveratrol (0.1-100 mumol/l). The EC50 values of the dose-response curves established for the inhibition of the sustained component of histamine-induced contractions were very similar to those obtained for the relaxations of fluoride-induced contractions: 0.45 +/- 0.08 and 0.29 +/- 0.05 mumol/l, resp. (n = 6). Ouabain (10 mumol/l)-induced contractions and rhythmic contractions elicited by tetraethylammonium (12 mmol/l) were also strongly inhibited by trans-resveratrol (20 mumol/l). It may be inferred from the results obtained in this study, that the relaxation of the coronary conductance vessels induced by trans-resveratrol is possibly based on a nongenomic interaction with steroid-like receptors located on the cell membrane.

The contribution of protein kinase C and CPI‐17 signaling pathways to hypercontractility in murine experimental colitis

Colonic smooth muscle contractility is altered in colitis, and several protein kinase pathways can mediate colonic smooth muscle contraction. In the present study, we investigated whether protein kinase C (PKC) pathways also play a role in colonic hypercontractility observed during T(H) 2 colitis in BALB/c mice. Colitis was induced in BALB/c mice by provision of 5% dextran sodium sulfate (DSS) for 7 days. Changes in smooth muscle contractility were examined using dissected circular smooth muscle preparations from the distal colon. The contribution of conventional and novel PKC isozymes to the hypercontractile response was examined with pharmacological PKC inhibitors. Western blot analyses were used to examine protein expression and phosphorylation changes. Colonic smooth muscle was associated with inflammation-induced hypercontractility and altered PKC expression. Carbachol-induced peak (phasic) and sustained (tonic) contractions were increased. Chelerythrine was the most effective PKC inhibitor of both phasic and tonic contractions. There was no general difference in the percent contribution of conventional and novel PKC isozymes toward the DSS-induced hypercontractility, but inhibition of sustained force with GF109203x was higher for inflamed muscle. The CPI-17 phosphorylation was equally suppressed in both normal and DSS conditions by Gö6976 and chelerythrine, but only for the phasic component of contraction. The outcomes suggest that both conventional and novel PKC isozymes contribute to the phasic and tonic contractile components of BALB/c colonic circular smooth muscle under normal conditions, with novel PKC isozymes having a greater contribution to the tonic contraction. However, no effect of inflammation was observed on the relative contribution of PKC and CPI-17 toward the observed hypercontractility.

Differential effects of myosin light chain kinase inhibition on contractility, force development and myosin light chain 20 phosphorylation of rat cervical and thoracic duct lymphatics

The intrinsic contractile activity of lymphatics varies in different regions of the body. We have previously shown that cervical lymphatics possess an inherently higher frequency but lower tone at a given pressure when compared to thoracic duct lymphatics. However, the molecular mechanisms modulating the contractile characteristics of these lymphatics are not well understood. Since myosin light chain 20 (MLC(20)) phosphorylation appears to underlie the tonic component of lymphatic contraction, we hypothesized that the thoracic duct would be more sensitive to the modulation of MLC(20) phosphorylation when compared to cervical lymphatics. To test our hypothesis, the contractile activities and MLC(20) phosphorylation of thoracic duct and cervical lymphatics were determined in the absence or presence of the specific myosin light chain kinase (MLCK) inhibitor ML-7 under both isobaric and isometric conditions. Addition of ML-7 at each concentration tested led to a decrease in tone in both vessel types. While ML-7 (10(-6) m) significantly reduced the phasic contraction frequency of cervical lymphatics, it completely stopped phasic contractions of thoracic duct at that concentration. Under isometric conditions the active peak and plateau components of tension were both significantly higher in thoracic duct compared to cervical lymphatics. ML-7 (10(-5) m) significantly decreased both the active peak and plateau tensions of thoracic duct, whereas only the active peak tension of cervical lymphatics was decreased. In thoracic duct MLC(20) di-phosphorylation, but not mono-phosphorylation, was significantly decreased with increasing transmural pressure, whereas in cervical vessels only at the higher pressures tested did MLC(20) di-phosphorylation decrease. ML-7 treatment of the thoracic duct caused a significant decrease in both the mono- and di-phosphorylated forms of MLC(20). However, in cervical vessels ML-7 treatment produced an increase in the mono-phosphorylated MLC(20) form while di-phosphorylated MLC(20) was significantly decreased. These data indicate that thoracic duct has an enhanced sensitivity to MLCK inhibition when compared to cervical lymphatics and while the status of the mono- and di-phosphorylation forms of MLC(20) affects both tonic and phasic components of lymphatic contractions, the pressure-dependent changes in tonic contractions are modulated by the status of the di-phosphorylation of MLC(20) in the lymphatics.

Effects of Intrastriatal and Systemic Microinjections of Nicotine on Motor Behavior and Its Motor and Postural Components in Dogs

In chronic experiments in dogs on a model of instrumental avoidance reflex we have found that intrastriatal and/or systemic injection of nicotine causes a significant prolonged increase of motor excitability. By decrease of latent period of instrumental reflex, an increase of amplitude of reflex was shown and, in some cases, by increase of conditional flexion maintenance time. An interesting feature of instrumental reflex in our investigations was both strengthening of cholinergic influence and strengthening of dopaminergic influence. The former is shown by sharp strengthening of tonic component of answer, the latter--by increase of answer amplitude and decrease of its latency, increase of general excitability.

Aging-Associated Alterations in Contractility of Rat Mesenteric Lymphatic Vessels

To evaluate the age-related changes in pumping of mesenteric lymphatic vessels in 9- and 24-month-old male Fisher-344 rats. Lymphatic diameters, contraction amplitude, contraction frequency, and fractional pump flow were determined in isolated MLV before and after l-NAME application. The data demonstrate a severe weakening of the lymphatic pump in aged MLV including diminished lymphatic contraction amplitude, contraction frequency, and as a result, lymphatic pump activity. The data also suggest that the imposed flow gradient-generated shear-dependent relaxation does not exist in aged rat MLV, and the sensitivity of both adult and aged MLV to such shear cannot be eliminated by nitric oxide (NO) synthases blockade. These data provide new evidence of lymphatic regional heterogeneity for both adult and aged MLV. In MLV, a constant interplay between the tonic and phasic components of the myogenic response and the shear-dependent release of NO predominantly determine the level of contractile activity; the existence of another shear-dependent, but NO-independent regulatory mechanism is probably present. Aging remarkably weakens MLV contractility, which would predispose this lymphatic network to lower total lymph flow in resting conditions and limit the ability to respond to an edemagenic challenge in the elderly.

Tonic and phasic components of eye movements during REM sleep in the rat

Phasic oculomotor activity is one of the features identifying rapid eye movement (REM) sleep. Recently, it has been shown in cats that, despite bursts of complex two-component rapid eye movements, the eyes tend to maintain a nasal and downward rotation during REM sleep. Although the function of eye movements during sleep remains elusive, it is important to know whether the characteristics of eye movements during sleep are species-specific in mammals. In this work, quantitative characteristics of eye movements, recorded by the scleral search coil technique, were studied during wakefulness and sleep in rats. During wakefulness, rats performed conjugated saccades at a very low rate and some eye movements associated to blinking and gnawing. Throughout non-REM sleep, eye movements were slow, mostly unconjugated and the eyes maintained a divergence in the horizontal plane. The beginning of REM sleep was characterized by a convergence and downward rotation of the eyes, which tended to persist until the end of REM sleep. Rapid eye movements, isolated and monocular at the beginning, became complex and organized in high-frequency bursts. These results demonstrate that, despite the difference in extraocular anatomy and visuomotor strategies between frontal- and lateral-eyed species, eye movements during REM sleep in rats are very similar to those described in cats. This suggests that the mechanisms generating eye movements during REM sleep are largely conserved in mammals.

Short-term adaptations of the dynamic disparity vergence and phoria systems

The ability to adapt is critical to survival and varies between individuals. Adaptation of one motor system may be related to the ability to adapt another. This study sought to determine whether phoria adaptation was correlated with the ability to modify the dynamics of disparity vergence. Eye movements from ten subjects were recorded during dynamic disparity vergence modification and phoria adaptation experiments. Two different convergent stimuli were presented during the dynamic vergence modification experiment: a test stimulus (4° step) and a conditioning stimulus (4° double step). Dynamic disparity vergence responses were quantified by measuring the peak velocity (°/s). Phoria adaptation experiments measured the changes in phoria over a 5-min period of sustained fixation. The maximum velocity of phoria adaptation was determined from an exponential fit of the phoria data points. Phoria and dynamic disparity vergence peak velocity were both significantly modified (P<0.001). The maximum velocity of phoria adaptation was significantly correlated with the changes in convergence peak velocity (r>0.89; P<0.001). There was a strong correlation between the ability to adaptively adjust two different oculomotor parameters: a tonic and dynamic component. Future studies should investigate additional interactions between these parameters, and the ability to adaptively change other oculomotor systems such as the saccadic or smooth pursuit system. Understanding the ability to modify phoria, dynamic disparity vergence, and other oculomotor parameters can yield insights into the plasticity of short-term adaptation mechanisms.

Neural mechanism of activity spread in the cat motor cortex and its relation to the intrinsic connectivity

Motor cortical points are linked by intrinsic horizontal connections having a recurrent network topology. However, it is not known whether neural activity can propagate over the area covered by these intrinsic connections and whether there are spatial anisotropies of synaptic strength, as opposed to synaptic density. Moreover, the mechanisms by which activity spreads have yet to be determined. To address these issues, an 8 × 8 microelectrode array was inserted in the forelimb area of the cat motor cortex (MCx). The centre of the array had a laser etched hole ∼500 μm in diameter. A microiontophoretic pipette, with a tip diameter of 2-3 μm, containing bicuculline methiodide (BIC) was inserted in the hole and driven to a depth of 1200-1400 μm from the cortical surface. BIC was ejected for ∼2min from the tip of the micropipette with positive direct current ranging between 20 and 40 nA in different experiments. This produced spontaneous nearly periodic bursts (0.2-1.0 Hz) of multi-unit activity in a radius of about 400 μm from the tip of the micropipette. The bursts of neural activity spread at a velocity of 0.11-0.24 ms⁻¹ (mean=0.14 mm ms⁻¹, SD=0.05)with decreasing amplitude.The area activated was on average 7.22 mm² (SD=0.91 mm²), or ∼92% of the area covered by the recording array. The mode of propagation was determined to occur by progressive recruitment of cortical territory, driven by a central locus of activity of some 400 μm in radius. Thus, activity did not propagate as a wave. Transection of the connections between the thalamus and MCx did not significantly alter the propagation velocity or the size of the recruited area, demonstrating that the bursts spread along the routes of intrinsic cortical connectivity. These experiments demonstrate that neural activity initiated within a small motor cortical locus (≤ 400 μm in radius) can recruit a relatively large neighbourhood in which a variety of muscles acting at several forelimb joints are represented. These results support the hypothesis that the MCx controls the forelimb musculature in an integrated and anticipatory manner based on a recurrent network topology

Evaluation of different drugs in two models of immediate hypersensitivity.

The effect of the calcium antagonists, verapamil, nicardipine and diltiazem, the two cromones, disodium cromoglycate and SM-857 (11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid), and the anthelmintic, diethylcarbamazine citrate, have been compared on the ovalbumin (OA)-induced contraction of the isolated trachea and longitudinal muscle-myenteric plexus (LM-MP) from sensitized guinea-pigs. The calcium antagonists prevented the OA-induced contractions in LM-MP and to a lesser degree the OA-induced contractions in trachea. Similar doses of SM-857 protected both tissues but neither cromoglycate (10(-5)M) nor diethylcarbamazine (10(-5)M) affected these contractions. The OA-induced contraction in trachea had a tonic phase that was not present in the LM-MP response. Only the calcium antagonists succeeded in relaxing this OA tonic component, diltiazem being the more potent. These results unmask different mechanisms of drug action on immediate hypersensitivity and specific sensibilities, depending on the kind of tissue.

Alerting, orienting and executive control: the effects of sleep deprivation on attentional networks

Sleep deprivation alters attentional functions like vigilance or tonic alerting (i.e., sustaining an alert state over a period of time). However, the effects of sleep loss on both orienting and executive control are still not clear, and no study has assessed whether sleep deprivation might affect the relationships among these three attentional systems. In order to investigate the efficiency of the three attentional networks--alerting, orienting and executive control--within a single task, we used the Attention Network Test (ANT). Eighteen right-handed male participants took part in the experiment, which took place on two consecutive days. On the first day, each participant performed a 20 min training session of the ANT. On the second day, participants remained awake for 24 h during which time the ANT was performed once at 5:00 p.m. and once at 4:00 a.m. Results showed an overall slowing of reaction times in the nocturnal session, indicating a strong decrease in vigilance. Furthermore, sleep deprivation did affect attentional orienting and executive control. Results are consistent with the hypothesis that the tonic component of alerting interacts with both attentional orienting and executive functions.

Daytime Sleepiness and REM Sleep Characteristics in Myotonic Dystrophy: A Case-Control Study

Excessive daytime sleepiness (EDS) and high daytime REM sleep pressure are important sleep features of myotonic dystrophy (DM1). Small and uncontrolled studies have focused on EDS phenotype; none have focused on nocturnal REM sleep characteristics in DM1. Our objectives were to compare polysomnographic and multiple sleep latency test (MSLT) parameters, and both tonic and phasic components of REM sleep between DM1 and controls. Forty consecutive DM1 patients and 40 sex- and age-matched controls were included. All subjects underwent overnight polysomnography followed by a MSLT. About 80% of DM1 patients complained of EDS through clinical interview: 31.4% had Epworth scores > 10, and 12.5% had objective sleepiness (latency < 8 min). Higher apnea and central apnea indexes, and a greater proportion of subjects with severe apnea/hypopnea syndrome were found in DM1. The number of SOREMP differed between DM1 and controls, one and two SOREMPs being present in 47.5% and 32.5%, and one control had one SOREMP. Higher percentages of slow wave sleep and REM sleep were found in DM1. DM1 patients had significantly more PLMW, PLMS in both NREM and REM sleep, and PLMS-associated microarousals. Higher REM density was found in DM1 with similar tendencies for either REM sleep without atonia or phasic EMG activity. This is the first case-control sleep study in DM1 to demonstrate higher frequency of daytime sleepiness and abnormalities in REM sleep regulation, with an increased daytime and nighttime REM sleep propensity, REM density, and PLMS. These data suggest a primary central sleep regulation dysfunction in DM1.