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PubMed1976

Plasma catecholamine levels in the coronary sinus, aorta and femoral vein of subjects undergoing cardiac catheterization at rest and during exercise.

Plasma catecholamine (CA) levels in the coronary sinus (CS), aorta (Ao) and femoral vein (fv) were simultaneously measured in 22 patients with various heart diseases at rest and during handgrip exercise (IHG). The mean resting levels of plasma norepinephine (NE) in CS, Ao and FV were 359 +/- 49 (SEM) pg/ml, 290 +/- 27 and 234 +/- 24, respectively. The corresponding values of epinephrine (E) were 127 +/- 18 pg/ml, 186+/- 30 and 97 +/- 11, respectively. The E values in Ao were significantly greater than those in CS and in FV (p less than 0.05). IHG exercise induced an obvious elevation of plasma CA levels in every portion of the circulation studied. The mean increments of NE concentration were 81%, 54% and 67% of the resting levels at CS, Ao and FV, respectively, while IHG induced elevation of E were 70% of the resting values at each portion studied. Significant correlations were observed between individual CA concentrations in CS and in Ao, and also between those in Ao and in FV at rest. Under raised sympathoadrenal conditions, however, individual values of NE in CS failed to correlate signficantly to those in Ao and in FV, respectively. The NE output from CS was limited to only 3% and 5% of those in Ao at rest and during IHG, respectively. An actual mean increment of NE on its passing through the coronary circulation was only 2% or less of NE output in ao at both stages. It appears, thus, to be untenable that the cardiac tissue is one of the major source of circulating CA at physiological condition. From these reasons, the direct measurement of NE levels in CS may be mandatory, when plasma CA assay is designed for the purpose of studying the role of the sympathetic nerve activity in the regulation of cardiac function.

Adolescent↗
PubMed1998

A case of variant angina pectoris with similar findings on both rest and matched exercise thallium-201 studies.

A patient with variant angina showed similar findings on both the rest and matched exercise 201Thallium (201Tl) myocardial perfusion scintigrams. The 65-year old man was admitted to hospital because of rest angina. His electrocardiogram during the attack disclosed ST segment elevation on inferior leads. However, emergency coronary arteriogram showed no fixed stenosis. Intracoronary injection of acetylcholine induced a spasm on the distal right coronary artery, but not in the left coronary artery. In the rest 201Tl study, septal perfusion was low on the early image, although partial redistribution of this site was observed on the delayed image without the appearance of chest pain or electrocardiographic ischemic change. Similary, in the 201Tl exercise study undergone 2 weeks later, septal redistribution was diagnosed because the early image had decreased septal perfusion. Both the exercise 123I-metaiodobenzylguanidine study and the rest 123I-betamethyl-p-iodophenyl-pentadecanoic acid study showed inferior abnormalities on the early and delayed images. Although a coronary spasm was not induced in the left anterior descending artery with the acetylcholine test, septal redistribution was observed on the delayed image of both the rest and exercise 201Tl studies. The mechanism of the redistribution on the rest 201Tl study was unclear.

Aged↗
PubMed2000

New combined spasm provocation test in patients with rest angina: intracoronary injection of acetylcholine after intracoronary administration of ergonovine.

The incidence of provoked coronary spasm with the standard single spasm provocation test has been relatively low in patients with rest angina. The present study examined the clinical usefulness of a newly designed spasm provocation test, an intracoronary injection of acetylcholine (ACh) following an ergonovine (ER) test, in patients with rest angina who demonstrated low disease activity and atypical chest pain. Triple sequential spasm provocation tests were performed in 24 patients with atypical chest pain who had no ischemia and in 40 patients with rest angina who had distinct ischemia. Initially, an ACh test (20-100 microg) and then an ER test (40-64 microg) were performed and then, if no spasm was provoked, an intracoronary injection of ACh was given after the ER test to evaluate coronary spasm. Coronary spasm was defined as total or subtotal occlusion. In the 24 patients with atypical chest pain, no spasm was provoked by intracoronary injection of either ACh or ER, but coronary spasms were induced in 2 patients using the new method, with the remaining 22 not experiencing spasm (specificity of new method, 92%). In the 40 patients with rest angina, intracoronary injection of ACh induced coronary spasm in 22 patients (group I) and 6 (group II) demonstrated spasm with intracoronary injection of ER. Coronary spasm was not induced by either the ACh test or the ER test in 12 patients (group III). The intracoronary administration of ACh after the ER test provoked spasm in 11 of 12 patients. Diffuse spasms were provoked in 10 of 11 patients. In patients with rest angina, the frequency of chest pain attacks in 1 month experienced by patients in group III (0.8+/-0.8) was significantly lower than that of patients in group I (7.0+/-5.3, p<0.01) or II (3.5+/-2.3, p<0.05). No serious or irreversible complications related to this new combined method were observed. In conclusion, this method was safe and reliable for the induction of coronary spasm in patients with rest angina who may have low disease activity.

Acetylcholine↗
PubMed2001

Resting ultrasonic tissue characterization and dobutamine stress echocardiography for prediction of functional recovery in chronic left ventricular ischemic dysfunction.

This study was designed to assess the diagnostic accuracy of the percentage of resting systolic wall thickening (WT), dobutamine stress echocardiography (DSE), resting cyclic variation of integrated backscatter (IBS-CV), and low-dose dobutamine stress IBS-CV (DSE-IB) for the prediction of regional function recovery (RFR) in patients with chronic left ventricular (LV) ischemic dysfunction. The study also evaluated whether or not global LV function affected the diagnostic accuracy. All studies were conducted before percutaneous transluminal coronary angioplasty (PTCA) and RFR was assessed after PTCA (mean interval, 10 months) in 30 patients with chronic LV ischemic dysfunction. Patients were divided into 2 groups according to the LV ejection fraction (LVEF): group A, LVEF<40%, n=14; group B, LVEF> or =40%, n=16. Of a total of 480 segments, 37 initially demonstrating akinetic wall motion before PTCA were analyzed. The wall motion of 24 of the 37 segments improved on visual analysis after PTCA. In the prediction of RFR, resting WT, DSE, resting IBS-CV and DSE-IB had sensitivities of 79%, 79%, 92% and 62%, and specificities of 54%, 84%, 83% and 69%, respectively. In particular, the resting IBS-CV in group A, as well as DSE, was an excellent predictor of RFR (sensitivity, 100%; specificity, 86%; vs sensitivity, 82%; specificity, 78%; respectively). Therefore, both resting IBS-CV and DSE are useful predictors for RFR in patients with chronic LV ischemic dysfunction.

Aged↗
PubMed2006

Cardiac re-synchronization therapy: effects on myocardial perfusion at rest, after vasodilation and oxygen consumption.

AIM: Cardiac resynchronization therapy (CRT) has been shown to improve haemodynamics and clinical symptoms in heart failure patients. The present study evaluated the effects of a 4-month CRT on myocardial blood flow (MBF) at rest, after vasodilation and on myocardial oxygen consumption (MVO(2)). PATIENTS, METHODS: We studied 16 patients with idiopathic dilated cardiomyopathy prior to and during CRT performed as biventricular pacing. Resting MBF and MVO(2) were determined from an (11)C-acetate PET study and vasodilator MBF from a (13)N-ammonia study. RESULTS: MBF at rest (0.55 +/- 0.10 ml/min/g), after vasodilation (1.20 +/- 0.45 ml/min/g), and MVO2 (0.082 +/- 0.014/min) did not change by mid-term CRT at a global level (0.57 +/- 0.11 ml/min/g; 1.32 +/- 0.49 ml/min/g; 0.085 +/- 0.018/min), whereas the rate pressure product (RPP) normalised MVO(2) decreased from 0.104 +/- 0.024 to 0.086 +/- 0.018/min (p = 0.02). At baseline, the regional analysis revealed significantly higher values for all parameters in the lateral wall than for those in the other walls. Under CRT the regional differences between the resting parameters equalized and all parameters showed significant lower coefficients of variation. CONCLUSION: Effects of mid-term CRT on resting MBF, vasodilator MBF and MVO(2) occur at a regional level. The resynchronization is associated with a more homogenous distribution pattern of these parameters among the myocardial walls. Substantial alterations to global MBF at rest, after vasodilation or to MVO(2) are not detectable. Regarding the RPP normalised MVO(2), there is evidence of improved ventricular efficiency through CRT.

Aged↗
PubMed2001

Calcium buffering of resting, voltage-dependent Ca2+ influx by sarcoplasmic reticulum in femoral arteries from spontaneously hypertensive rats at prehypertensive stage.

We examined the Ca2+-buffering function of the sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) at a prehypertensive stage. Differences in the effects of cyclopiazonic acid (CPA) and thapsigargin, agents that inhibit SR Ca2+-ATPase, and of ryanodine, which depletes SR Ca2+, on tension and cellular Ca2+ level were assessed in endothelium-denuded strips of femoral arteries from 4-week-old SHR and normotensive Wistar-Kyoto rats (WKY). Addition of CPA, thapsigargin or ryanodine to the resting state of the strips caused an elevation of cytosolic Ca2+ level and a contraction in both WKY and SHR. These responses were larger in SHR than in WKY. The contractions were inhibited strongly by 100 nM nifedipine or 3 microM verapamil and were abolished by Ca2+-free solution. Nifedipine, verapamil or Ca2+-free solution itself caused a relaxation from the resting state of SHR strips, but not from that of WKY strips. The resting Ca2+ influx in arteries measured by a 5-min incubation with 45Ca was significantly larger in SHR than in WKY. This influx was decreased by 10 microM CPA or 10 microM ryanodine in both WKY and SHR. These results suggest that in the resting state of the femoral artery from 4-week-old SHR, the greater part of the increased Ca2+ influx via L-type Ca2+ channels is buffered by Ca2+ uptake into the SR, while some Ca2+ reaches the myofilaments, resulting in the maintenance of resting tone.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Augmented resting sympathetic activity in awake patients with obstructive sleep apnea.

Muscle nerve sympathetic activity (MSA) was recorded during wakefulness in 11 patients with obstructive sleep apnea (OSA) and in 9 sex- and age-matched healthy control subjects. Plasma levels of norepinephrine (NE) and neuropeptide Y were analyzed. Five patients had established hypertension (resting supine systolic BP/diastolic BP > or = 160/95 mm Hg). The investigation was performed after a minimum of 3 weeks' washout period of antihypertensive medication. Muscle sympathetic activity during supine rest was higher in patients compared with controls (p < 0.01) with no difference between normotensive and hypertensive patients. However, systolic, but not diastolic, BP was positively related to resting MSA (n = 20, p < 0.01). There was no significant correlation between body mass index and MSA. Resting MSA was unrelated to disease severity expressed as apnea frequency or minimum SaO2 during the overnight recording. Both the arterial and venous plasma norepinephrine was higher in patients compared with controls (p < 0.05). Plasma levels of NE correlated to resting MSA (p < 0.01) in the whole study group (patients and controls) but not within the respective subgroups. No significant correlation, however, was found between plasma NE (arterial and venous) and BP. Plasma neuropeptide Y-like immunoreactivity was similar in patients and controls. However, one patient with hypertension had approximately twice this level in repeated samples. It is concluded that neurogenic sympathetic activity as well as circulating plasma NE is increased in patients with OSA. This increased sympathetic activity during awake supine rest may reflect a pathophysiologic adaptation to hypoxia and hemodynamic changes occurring at repetitive apneas during sleep. The correlation between MSA and systolic BP implies that this mechanism may be directly or indirectly involved in the development of cardiovascular complications in OSA.

Adult↗
PubMed2006

Steady-state adaptation of mechanotransduction modulates the resting potential of auditory hair cells, providing an assay for endolymph [Ca2+].

The auditory hair cell resting potential is critical for proper translation of acoustic signals to the CNS, because it determines their filtering properties, their ability to respond to stimuli of both polarities, and, because the hair cell drives afferent firing rates, the resting potential dictates spontaneous transmitter release. In turtle auditory hair cells, the filtering properties are established by the interactions between BK calcium-activated potassium channels and an L-type calcium channel (electrical resonance). However, both theoretical and in vitro recordings indicate that a third conductance is required to set the resting potential to a point on the I(Ca) and I(BK) activation curves in which filtering is optimized like that found in vivo. Present data elucidate a novel mechanism, likely universal among hair cells, in which mechanoelectric transduction (MET) and its calcium-dependent adaptation provide the depolarizing current to establish the hair cell resting potential. First, mechanical block of the MET current hyperpolarized the membrane potential, resulting in broadband asymmetrical resonance. Second, altering steady-state adaptation by altering the [Ca2+] bathing the hair bundle changed the MET current at rest, the magnitude of which resulted in membrane potential changes that encompassed the best resonant voltage. The Ca2+ sensitivity of adaptation allowed for the first physiological estimate of endolymphatic Ca2+ near the MET channel (56 +/- 11 microM), a value similar to bulk endolymph levels. These effects of MET current on resting potential were independently confirmed using a theoretical model of electrical resonance that included the steady-state MET conductance.

Adaptation, Physiological↗
PubMed2001

Metabolic habituation following repeated resting cold-water immersion is not apparent during low-intensity cold-water exercise.

This project examined the effects of repeated, resting cold-water immersion on metabolic heat production and core temperature defence during subsequent rest and exercising immersions. Seven males undertook 15 days of cold-water adaptation, immersed to the fourth intercostal space, with cold-water stress tests (CWST) on days 1, 8 and 15 (18.1 SD 0.1 degree C: 60 min seated, followed by 30 min cycling (1 W.kg-1)), and 90-min resting immersions (18.4 SD 0.4 degree C) on each of the intervening days. Adaptation elicited an habituated thermogenic response during the rest phase of CWST3 beyond 20 min, compared to CWST1 (P < 0.05), with oxygen consumption averaging 11.15 (+/- 0.25) ml.kg-1.min-1 and 8.61 (+/- 0.90) ml.kg-1.min-1 by 50 min, for CWST1 and CWST3, respectively. During exercise, this metabolic blunting was only apparent over the first 10-min period (60-70 min). No significant differences were observed during either the rest or exercise phases of the CWSTs for oesophageal temperature (Tes). While repeated cold-water exposures produced an habituated-thermogenic response, for an equivalent drop in Tes during rest, neither this response, nor an elevated thermogenesis, were apparent during subsequent cold-water exercise.

Adaptation, Physiological↗
PubMed1982

Post-rest adaptation of electrical and mechanical activity in the isolated guinea-pig papillary muscle.

In guinea-pig papillary muscle the time course of the changes in contractile force and action potential duration (APD) were studied after periods of rest of variable duration. After a long period of rest, the force of contraction adapted to pre-rest control values in a monophasic manner whereas the time-course of the APD was clearly biphasic. The post-rest adaptation of the APD could be described mathematically by a simple model, which considers the action potential duration during steady state as the sum of a resting value (APDR) plus a lengthening effect of activation (LEA) minus a shortening effect of activation (SEA). LEA and SEA are assumed to occur immediately, with each excitation and to decay continuously. During repetitive stimulation, both effects will accumulate. Using the constants found for the post-rest adaptation of the APD, the steady-state frequency-dependence of the APD could also be described with this model.

Action Potentials↗
PubMed2003

Coexpression of CD58 or CD48 with intercellular adhesion molecule 1 on target cells enhances adhesion of resting NK cells.

The beta2 integrin LFA-1 (CD11a/CD18) mediates adhesion of lymphocytes to cells expressing ICAM. The strength of this adhesion is regulated by different signals delivered by cytokines and chemokines, and by the TCR in the case of T cells. To determine the receptor-ligand interactions required for adhesion of resting NK cells, Drosophila cells expressing different combinations of ligands of human NK cell receptors were generated. Expression of ICAM-1 alone was sufficient for an adhesion of resting NK cells that was sensitive to inhibitors of src family kinase and of phosphatidylinositol 3-kinase. Binding of resting NK cells to solid-phase ICAM-1 showed similar signaling requirements. A pulse of either IL-2 or IL-15 to resting NK cells resulted in strongly enhanced, actin-dependent adhesion to insect cells expressing ICAM-1 alone. Coexpression of either LFA-3 (CD58) or CD48 with ICAM-1 resulted in strong adhesion by resting NK cells, even in the absence of cytokines. Therefore, receptors for LFA-3 and CD48 on resting NK cells strengthen the adhesion mediated by LFA-1.

Adjuvants, Immunologic↗
PubMed1999

Requirement for efficient interactions between CD4 and MHC class II molecules for survival of resting CD4+ T lymphocytes in vivo and for activation-induced cell death.

Regulation of homeostasis in the immune system includes mechanisms that promote survival of resting T lymphocytes, and others that control activation-induced cell death (AICD). In this study, we report on the use of a transgenic mouse model to test the role of CD4-MHC class II interactions for the susceptibility of CD4+ T lymphocytes to AICD, and for the survival of resting CD4+ T cells in peripheral lymphoid organs. The only I-Abeta gene expressed in these mice is an Abetak transgene with a mutation that prevents MHC class II molecules from interacting with CD4. We show increased apoptosis in CD4+ T lymphocytes derived from wild-type, but not from mutant Abetak transgenic mice following stimulation with staphylococcal enterotoxin A. Therefore, AICD may be impaired in CD4+ T cells derived from mutant Abetak transgenic mice. Importantly, we observed much higher apoptosis in resting CD4+ T cells from mutant Abetak transgenic mice than from wild-type mice. Furthermore, resting CD4+ T cells from mutant Abetak transgenic mice expressed higher levels of cell surface CD95 (Fas, APO-1). Ab-mediated cross-linking of CD95 further increased apoptosis in CD4+ T cells from mutant Abetak transgenic mice, but not from wild-type mice, suggesting apoptosis involved CD95 signaling. When cocultured with APC-expressing wild-type MHC class II molecules, apoptosis in resting CD4+ T lymphocytes from mutant Abetak transgenic mice was reduced. Our results show for the first time that interactions between CD4 and MHC class II molecules are required for the survival of resting CD4+ T cells in peripheral lymphoid organs.

Animals↗
PubMed1999

The effects of rest interval on quadriceps torque and perceived exertion in healthy males.

BACKGROUND: The ability to generate maximal muscular force is dependent upon time mediated mechanisms of fatigue. Interset rest interval length may not only affect force production but may also manifest changes in ratings of perceived exertion (RPE). The purpose of this study was to examine the effects of rest interval on quadriceps torque and RPE during multiple sets of resisted knee extensions. METHODS: 14 healthy male volunteers were assessed for concentric isokinetic quadriceps peak torque, total work, and average power on the Biodex System II Isokinetic Dynamometer at a preset angular velocity of 180 deg.sec-1. Perceived exertion was measured with a modified category-ratio scale (CR-10). Under isometric conditions the perceptual range was anchored with one high and two low anchors. Subjects were randomly assigned to one of two groups: short rest interval (Group 1, 40 sec) and long rest interval (Group 2, 160 sec). All subjects performed 4 sets of 20 maximal isokinetic contractions with an inter-set rest interval that corresponded to their group assignment. Following the completion of each set subjects were asked to assign a rating out of 10 to the feelings in their quadriceps by visually observing a chart of the CR-10 scale. RESULTS: The results demonstrated a significantly greater decline in quadriceps peak torque (p < 0.05), total work (p < 0.05), and average power (p < 0.05) by Group 1 as compared to Group 2. Changes in RPE across the 4 sets of exercise did not show a significant difference between the 2 groups. CONCLUSIONS: The generation of quadriceps torque is a function of rest interval length, whereas perceived exertion appears to be unaffected.

Adult↗
PubMed2000

[Postnatal care--sleep, rest and satisfaction].

BACKGROUND: During the last decade most hospitals in Norway have introduced breastfeeding according to the baby's needs during night-time as well. The aim of this study was to examine whether women had sufficient sleep and rest in the maternity unit, and the factors influencing insufficient sleep and rest. The degree of satisfaction with the stay in the maternity unit and factors associated with satisfaction were also studied. MATERIAL AND METHODS: From April to November 1998, 160 postnatal women in two Norwegian communities were included in a questionnaire-based study, representing 89% of all women eligible for the study. RESULTS: 47% (75/160) of the women reported lack of sleep and rest in the maternity unit. The factor most strongly associated with lack of sleep and rest was not having a single room (adjusted odds ratio 11.0; 95% confidence interval: 1.7-69.1). 56% (88/158) of the women reported to be very satisfied, 39% (68/158) were moderately satisfied, and 5% (8/158) dissatisfied with the stay at the maternity unit. Not being very satisfied was associated with the hospital of delivery (adjusted OR 18.0; 95% CI: 2.2-149.1), and with insufficient sleep and rest (OR 3.3: 1.3-8.1). INTERPRETATION: Our results suggest that women do not get sufficient sleep and rest under existing circumstances in maternity units.

Adult↗
PubMedDate not supplied

The effects of buccolingual width and position of occlusal rest seats on load transmission to the abutments for tooth-supported removable partial dentures.

PURPOSE: The suitable buccolingual width and the location of occlusal rest seats for removable partial dentures have not been scientifically established. The aim of the present study was to use three-dimensional geometric analysis to evaluate the effects of buccolingual width and the location of occlusal rest seats on load transmission to the abutments for tooth-supported removable partial dentures. MATERIALS AND METHODS: A tooth-supported portion of a maxillary removable partial denture with two conventional circumferential cast clasps and an indirect retainer was analyzed. Occlusal loading of 100 N was applied to the buccal mesial cuspal incline 2.0 mm from the central fossa of the first molar or to the lingual mesial cuspal tip. Four combinations of position and width (wide, buccal shift, middle, and lingual shift) were simulated. RESULTS: For buccal loading, the wide rests and buccal-shift rests produced lower tensile forces at the indirect retainer. For lingual loading, the buccal-shift rests produced the lowest compressive force to the anterior abutment. CONCLUSION: Based on the tooth-supported removable partial dentures that were analyzed, buccal shifting of the rest seats seems to be advantageous for load transmission to the abutments.

Bicuspid↗
PubMed2002

Myocardial contractile reserve and perfusion defect severity with rest and stress dobutamine (99m)Tc-sestamibi SPECT in canine stunning and subendocardial infarction.

UNLABELLED: Myocardial contractile reserve and resting perfusion scintigraphy provide independent information to assess myocardial viability. The purpose of this study was to simultaneously evaluate both with (99m)Tc-sestamibi SPECT and low-dose dobutamine in canine stunning and subendocardial infarction (SEMI). METHODS: Eighteen dogs were included in the study: 7 normal, 7 stunned, and 4 with SEMI. Closed-chest stunning and SEMI were produced by angioplasty balloon occlusion of the left anterior descending artery (20 and 90 min, respectively). Subsequent radiolabeled mircospheres confirmed reflow, and (99m)Tc-sestamibi was then administered at rest. Gated SPECT and MRI tagging were performed at rest and during low-dose dobutamine infusion (5 microg/kg/min). SPECT systolic wall thickening index (SWI) and MRI radial strain quantified myocardial contraction. Postmortem 2,3,5-triphenyltetrazolium chloride staining quantified SEMI. RESULTS: Defect severity by SPECT in the anterior wall was mild and was not statistically different for the stunned versus SEMI groups (P = not significant). At rest, anterior wall SPECT SWI was significantly higher in the normal versus stunned groups (21.1 +/- 3.1 vs. 10.1 +/- 9.0; P = 0.0002) and the normal versus SEMI groups (21.1 +/- 3.1 vs. 2.6 +/- 6.0; P = 0.000002). With low-dose dobutamine, SWI increased significantly compared with rest for the stunned group (29.1 +/- 10.4 vs. 10.1 +/- 9.0; P = 0.000007) but did not increase significantly for the SEMI group (11.0 +/- 11.3 vs. 2.6 +/- 6.0; P = 0.09); SWI during low-dose dobutamine infusion for the stunned group was comparable to that for the normal group (29.1 +/- 10.4 vs. 28.2 +/- 7.0; P = 0.80). SWI also showed correlation with MRI radial strain (r = 0.42; P = 0.00015). CONCLUSION: Defect severity for stunned myocardium and SEMI was mild and was not significantly different. Contractile reserve was significantly different in stunned myocardium and SEMI. (99m)Tc-Sestamibi SPECT at rest and with low-dose dobutamine is a promising new technique to simultaneously assess myocardial perfusion and contractile reserve.

Animals↗
PubMed2003

Ischemic insults derepress the gene silencer REST in neurons destined to die.

A subset of genes implicated in genetic and acquired neurological disorders encode proteins essential to neural patterning and neurogenesis. The gene silencing transcription factor neuronal repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) plays a critical role in elaboration of the neuronal phenotype. In neural progenitor and non-neural cells, REST acts by repression of a subset of neural genes important to synaptic plasticity and synaptic remodeling, including the AMPA receptor (AMPAR) subunit GluR2. Here we show that global ischemia triggers REST mRNA and protein expression. REST suppresses GluR2 promoter activity and gene expression in neurons destined to die. Because the GluR2 subunit governs AMPAR Ca2+ permeability, these changes are expected to have profound effects on neuronal survival. In keeping with this concept, acute knockdown of the REST gene by antisense administration prevents GluR2 suppression and rescues post-ischemic neurons from ischemia-induced cell death in an in vitro model. To our knowledge, our study represents the first example of ischemia-induced induction of a master transcriptional regulator gene and its protein expression critical to neural differentiation and patterning in adult neurons. Derepression of REST is likely to be an important mechanism of insult-induced neuronal death.

Animals↗
PubMedDate not supplied

[The development of the concept of neuronal resting potential. Fundamental and clinical aspects].

INTRODUCTION AND AIMS: Since the classical works carried out on the squid giant axon far less attention has been directed towards the study of the resting membrane potential than to the study of changes in potential (action potential, synaptic potentials, and so forth). It is often assumed that the resting potential depends on an independent current of the voltage called the leakage current, although, except on rare occasions, it has not been possible to characterise such a current either pharmacologically or molecularly. In this work our aim is to review and update the concept of resting potential. DEVELOPMENT: The outlook at present offers a complex situation in which several factors, in addition to leakage currents, play a role in maintaining resting potentials. These factors include ionic currents across non-inactivating voltage-dependent channels, the sodium/potassium pump, and certain currents with characteristics that are similar to those of the classical leakage current. The interaction of all these components gives rise to complex sub-threshold behaviours in the neurons, such as intrinsic rhythmic oscillations, which leads us away from the passive concept of the resting potential. CONCLUSIONS: An ever-increasing number of descriptions of intrinsic sub-threshold, rhythmic activity are being reported, which could suggest that they are a generalised phenomenon in the nervous system. Further studies need to be conducted into the complex mechanisms that determine the resting potential in order to gain an understanding of the phenomena of neuronal excitability and to find an explanation for some of the many pathological conditions that affect the nervous system.

Action Potentials↗