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At least 19 recordsLinked to original sources

Fat-suppressed T2-weighted MRI of the liver: comparison of respiratory-triggered fast spin-echo, breath-hold single-shot fast spin-echo, and breath-hold fast-recovery fast spin-echo sequences.

The purpose of our study was to compare the value of respiratory-triggered fast spin-echo, breath-hold single-shot fast spin-echo, and breath-hold fast-recovery fast spin-echo sequences in detecting hepatic lesions. Fat-suppressed T2-weighted magnetic resonance (MR) images obtained with the three sequences in 36 patients with 138 lesions and nine patients without lesions were prospectively analyzed. Quantitative and qualitative analyses, including receiver operating characteristic (ROC) analyses, were performed. The mean lesion-to-liver contrast-to-noise ratio (CNR) for hepatic lesions was highest with the respiratory-triggered fast spin-echo sequence. On the basis of receiver-operating characteristic analyses, tumor detection rates were higher with the breath-hold fast-recovery fast spin-echo sequence (Az = 0.94) than with the respiratory-triggered fast spin-echo sequence (AZ = 0.80, P < 0.0001) or the single-shot fast spin-echo sequence (Az = 0.77, P < 0.0001). The image quality with the breath-hold fast-recovery fast spin-echo sequence was acceptable in all patients. The breath-hold fast-recovery fast spin-echo sequence provided the highest tumor detection in a short imaging time, although the mean lesion-to-liver CNRs were inferior to those of the respiratory-triggered fast spin-echo and the breath-hold single-shot fast spin-echo sequences.

Adult↗

Liver: T2-weighted MR imaging with breath-hold fast-recovery optimized fast spin-echo compared with breath-hold half-Fourier and non-breath-hold respiratory-triggered fast spin-echo pulse sequences.

At liver magnetic resonance (MR) imaging in 38 patients, a breath-hold T2-weighted fast spin-echo (SE) pulse sequence optimized with fast recovery was compared with a conventional respiratory-triggered fast SE sequence and a breath-hold single-shot fast SE sequence. Mean signal-to-noise ratios for liver and contrast-to-noise ratios for hepatic lesions were higher with the breath-hold fast-recovery fast SE sequence than with the respiratory-triggered fast SE sequence (P <.05). Breath-hold fast-recovery images displayed better lesion clarity than did single-shot fast SE images (P <.05) and fewer image artifacts than did respiratory-triggered fast SE images (P <.05). The ability to determine lesion size and the overall image quality was best with the breath-hold fast-recovery sequence (P <.05). These results may justify use of the breath-hold fast-recovery fast SE pulse sequence for first-line T2-weighted MR imaging of the liver.

Adult↗

TNF-alpha and heat-shock protein gene expression in ischemic-injured liver from fasted and non-fasted rats. Role of donor fasting in the prevention of reperfusion injury following liver transplantation.

We have previously shown that livers from long-term-fasted rats acquire tolerance to warm ischemic injury following transplantation, despite the fact that fasting depletes glycogen and ATP from the liver. The precise mechanism of the protective effect induced by donor fasting, however, is still a matter of controversy. In this experiment we determined heat-shock protein (GRP78) mRNA expression in livers during long-term fasting and TNF-alpha mRNA expression in transplanted livers exposed to warm ischemia. We also measured the concentration of TNF-alpha by ELISA in the ascitic fluid of fed and fasted rats injected intraperitoneally with zymosan to investigate why livers from fasted rats tolerate ischemic injury better. There seemed to be a positive correlation between GRP78 mRNA expression and survival. TNF-alpha secretion into the ascitic fluid of fasted rats was markedly suppressed, and fasting donor animals induced cytoprotective substances, such as GRP78, in the liver. These factors may contribute to the tolerance to ischemic injury produced by donor fasting.

Animals↗

Breath-hold fast recovery fast spin echo versus conventional non-breath-hold fast spin echo T2-weighted MR imaging of focal liver lesions.

INTRODUCTION: We compare the breath-hold fast recovery fast spin echo (BHFRFSE) T2-weighted and non-breath-hold fast spin echo (NBHFSE) T2-weighted sequences in image quality and lesion characterisation of focal liver lesions. MATERIALS AND METHODS: Fat-suppressed T2-weighted magnetic resonance (MR) images obtained with the 2 sequences (BHFRFSE and NBHFSE) in 79 patients with 113 liver lesions were analysed retrospectively. The image quality and nature of the lesions were evaluated by 2 experienced radiologists. RESULTS: Based on receiver operating characteristic curve analysis, lesion characterisation was comparable for both sequences. The image quality of BHFRFSE was significantly better than that of NBHFSE. The NBHFSE missed 4 malignant lesions while BHFRFSE missed 2 malignant lesions. CONCLUSION: BHFRFSE performs similarly to NBHFSE in image quality and liver lesion characterisation.

Adult↗

T2-weighted MRI of the female pelvis: comparison of breath-hold fast-recovery fast spin-echo and nonbreath-hold fast spin-echo sequences.

In 49 patients who had pelvic abnormalities, breath-hold T2-weighted fast-recovery (FR)-fast spin-echo (FSE) (imaging time = 24 sec) and nonbreath-hold FSE MR images (2 min 8 sec) were compared qualitatively (on a four-point scale) and quantitatively (using signal-to-noise ratios (SNRs) and contrast ratios (/SIs of the lesions-SIs of the myometrium/SIs of the myometrium)). Motion artifacts were reduced on breath-hold FR-FSE (3.8:3.2 = breath-hold FSE:nonbreath-hold FSE, P < 0.01) and image quality was comparable (3.8:3.7, NS). In all patients, pathology (leiomyoma [N = 26], adenomyosis [N = 10], endometrial carcinoma [N = 8], and ovarian cystic lesions [N = 21]) was recognized with comparable lesion conspicuity (3.8:3.7, NS) and better delineation of the structures (3.9:3.6, P < 0.05) on the FR-FSE images. There was no significant difference in contrast ratios, although SNRs (e.g., myometrium 18.3:25.8, P < 0.01) were better and the uterine zonal anatomy was recognized better on the nonbreath-hold FSE (3.4:3.7, P < 0.05). These differences did not affect the diagnosis. Breath-hold FR-FSE provides the benefits of motionless imaging and a short examination time, although lower SNRs were noted. J. Magn. Reson. Imaging 2001;13:930-937.

Adolescent↗

Differential effects of adenosine on antegrade fast pathway, antegrade slow pathway, and retrograde fast pathway in atrioventricular nodal reentry.

Adenosine has a potent negative dromotropic effect. However, comparative effects of adenosine on the three pathways of atrioventricular (AV) nodal reentry remain unclear. In this study, we sought to determine the effects of adenosine on the antegrade fast, antegrade slow, and retrograde fast pathway conduction in patients with AV nodal reentrant tachycardia (AVNRT). Twenty patients with common slow-fast AVNRT (mean cycle length 360 +/- 49 ms) were studied. The effects of adenosine on the antegrade slow pathway and on the retrograde fast pathway conduction were determined during sustained AVNRT and constant right ventricular pacing at identical cycle lengths (mean 360 +/- 49 ms), respectively. Incremental doses of adenosine were rapidly administered: initial dose of 0.5 mg, followed by stepwise increases of 0.5 or 1.0 mg given at 5-min intervals until termination of AVNRT or second-degree ventriculoatrial block occurred. After the antegrade slow pathway conduction was selectively and completely ablated by radiofrequency catheter ablation, the effect of adenosine on the antegrade fast pathway conduction was evaluated. The dose-response curve of adenosine and the dose of adenosine required to produce AV or ventriculoatrial block among the representative three conduction pathways were compared. The dose-response curve for the effect of adenosine on the antegrade fast pathway lies to the left and upward to that of the effect of adenosine on the antegrade slow pathway which in turn lies to the left and upward to that of the retrograde fast pathway. The mean dose of adenosine required to produce conduction block at antegrade fast, antegrade slow, and retrograde fast pathways were 1.4 +/- 0.5, 4.2 +/- 1.6, and 8.5 +/- 2.6 mg, respectively (p < 0.01). Adenosine has a differential potency to depress antegrade fast, antegrade slow, and retrograde fast pathway conduction in patients with AVNRT. The depressant effect of adenosine on the antegrade fast pathway is more potent than that on the antegrade slow pathway which in turn is more potent than that on the retrograde fast pathway conduction.

Adenosine↗

Higher fasting insulin but lower fasting C-peptide levels in African Americans in the US population.

BACKGROUND: Fasting serum insulin and fasting serum C-peptide are risk factors for developing type 2 diabetes. Because of the higher incidence of type 2 diabetes in African Americans and Hispanic Americans, it is likely that these groups may differ from non-Hispanic whites in their levels of insulin and C-peptide. METHODS: We analyzed data from a nationally representative sample of adults in the US population for whom sociodemographic, clinical, and laboratory information were obtained. The data were used to describe distributions of fasting insulin and fasting C-peptide in non-Hispanic white, non-Hispanic black, and Mexican American men and women aged >or=20 years without a medical history of diabetes. RESULTS: Among men, Mexican Americans had higher insulin values than non-Hispanic whites and blacks. Among women, both Mexican Americans and blacks had higher insulin values than whites. For C-peptide, differences by sex and race-ethnicity paralleled those seen for fasting insulin with the exception that black men had significantly lower C-peptide values than whites and Mexican Americans. After adjustment for age, fasting plasma glucose (FPG), body mass index (BMI), and waist-to-hip ratio (WHR), the higher levels for insulin in blacks and Mexican Americans remained; both black men and women had significantly lower C-peptide values than whites and Mexican Americans. The molar ratio of fasting C-peptide to fasting insulin was similar for men and women in each race-ethnic group. However, blacks had substantially lower ratios than whites and Mexican Americans. CONCLUSIONS: We found wide variations in fasting insulin and fasting C-peptide levels by race and ethnicity in US adults that were not explained by confounding factors, primarily measures of obesity. Most notably, the higher fasting insulin and lower fasting C-peptide levels in blacks implies that there is a derangement in insulin clearance and an impairment in beta-cell function in blacks compared with whites and Mexican Americans.

Adult↗

Force/velocity curves of fast oxidative and fast glycolytic parts of rat medial gastrocnemius muscle vary for concentric but not eccentric activity.

The purpose of this study was to compare the force exerted by the rat medial gastrocnemius (GM) muscle with either fast oxidative or fast glycolytic parts active during concentric and eccentric contractions at different velocities. The proximal end of the GM contains mainly fast oxidative fibres and the distal end predominantly fast glycolytic fibres. Different parts of GM were activated by selective stimulation of nerve branches. Fast oxidative or fast glycolytic muscle parts of anaesthetised male Wistar rats were activated maximally. After assessment of concentric force/velocity (F/v) relations (n=11), some of the muscles were subjected to a fatiguing series of isometric contractions (n=5). Fast oxidative muscle parts showed a significantly lower mean (+/-SD) maximal power output (P(max) 0.12+/-0.06 W) and fatigability than fast glycolytic muscle parts (P(max) 0.20+/-0.06 W). The remaining muscles performed eccentric contractions. The eccentric F/v curves were not significantly different for fast oxidative and fast glycolytic muscle parts (n=6). Maximum eccentric force relative to the maximum isometric force (157+/-3% and 153+/-6% respectively,P=0.99) was reached at a velocity of 60 mm s(-1). It is concluded that eccentric F/v relations of rat GM with either fast oxidative or fast glycolytic parts active are very similar despite the differences in the concentric F/v relations.

Animals↗

Diagnostic utility of fasting versus non-fasting blood glucose: contextualising testing strategies-a narrative review.

Diabetes mellitus is a chronic metabolic disorder characterised by impaired glucose homeostasis, resulting in persistent hyperglycaemia. Accurate and prompt diagnosis is essential for early intervention and prevention of long-term complications. Fasting blood glucose levels have traditionally been central to the diagnosis and monitoring of diabetes mellitus. However, growing evidence highlights the clinical relevance of non-fasting glucose measures, including postprandial glucose, random plasma glucose, and glycated haemoglobin (HbA1c) levels. Practical challenges, safety concerns, and evolving insights into glucose physiology have prompted renewed interest in flexible and context-driven approaches to glucose testing. This narrative review examines the physiological basis of fasting and non-fasting glucose regulation and critically evaluates their roles in diabetes screening, diagnosis, and monitoring. It also discusses the strengths and limitations of measuring fasting blood glucose, oral glucose tolerance, HbA1c, random plasma glucose, postprandial glucose, and continuous glucose monitoring. Special attention is given to pre-analytical and practical considerations, patient safety, and the ability of non-fasting measures to capture early metabolic dysfunction and real-world glycaemic exposure. This article reviews evidence supporting the prognostic value of postprandial hyperglycaemia and the expanding role of non-fasting monitoring tools. Non-fasting glucose testing offers substantial advantages in terms of accessibility, safety, and clinical relevance, and is well-suited for population screening and routine diabetes monitoring. Fasting glucose testing remains essential for specific diagnostic and research applications, particularly when strict metabolic standardisation is required. A context-driven framework that prioritises non-fasting approaches while reserving fasting tests for targeted indications provides a balanced and patient-centred strategy for contemporary diabetes care.

Diabetes screening↗

MR diagnosis of bone contusions of the knee: comparison of coronal T2-weighted fast spin-echo with fat saturation and fast spin-echo STIR images with conventional STIR images.

OBJECTIVES: Bone contusions consist of posttraumatic marrow change resulting from a combination of hemorrhage, edema, and microtrabecular injury and are depicted on MR images as geographic, nonlinear areas of abnormally increased T2 marrow signal intensity. Detection of bone contusions is important, not only in that they are frequently a sign of more serious associated injury, but in that isolated contusions may account for clinical symptoms and thereby obviate further workup. We evaluated two promising rapid imaging sequences, T2-weighted fast spin-echo with fat saturation and fast spin-echo short inversion time (T1) inversion recovery (STIR) and compared their efficacy to that of conventional STIR for the diagnosis of bone contusions in knees. SUBJECTS AND METHODS: Fifty-one consecutive military, retired military, and military-dependent patients were prospectively entered. Imaging consisted of three experimental sequences: coronal T2-weighted fast spin-echo with spectroscopic fat saturation, fast spin-echo STIR, and STIR, as well as conventional T1, proton density, and T2. Each examination was interpreted by three radiologists, for a total of 153 interpretations. Each interpretation consisted of the conventional sequences plus one of the three experimental sequences, blinded to the other two, specifically addressing menisci, ligaments, bones, and soft tissues. A positive test result was defined as a diagnosis of bone contusion on any one of the three independent interpretations of a given examination. Our gold standard was the consensus opinion of all three radiologists in a retrospective, unblinded evaluation of all imaging sequences. Sensitivity and specificity of fast spin-echo with fat saturation and fast spin-echo STIR were then calculated and compared with STIR. RESULTS: Sensitivity and specificity for bone contusion diagnosis in the three experimental sequences were as follows: fast spin-echo with fat saturation, 91% sensitivity and 86% specificity; fast spin-echo STIR, 96% sensitivity and 96% specificity; and conventional STIR, 83% sensitivity and 93% specificity. Our results showed no statistically significant difference between either of the fast spin-echo sequences and conventional STIR (p > .05). CONCLUSION: Because of their comparable accuracy and short imaging time characteristics, coronal fast spin-echo with fat saturation and fast spin-echo STIR sequences are superior to conventional STIR sequences for the diagnosis of bone contusions in knees.

Adolescent↗

The effect of fasting, transit plus fasting, and administration of adrenocorticotropic hormone on the source and amount of weight lost by feeder steers of different ages.

Two trials (winter and summer) were conducted to determine effects of fasting and transportation and adrenocorticotropic hormone (ACTH) administration on the amount and source of weight lost by feeder steers. Sixteen steers, in each of two experiments, were adapted to metabolism stalls for 10 d, were fed medium-quality hay at 2.1% of BW for 3 d, and then were subjected to either fasting alone or fasting plus transit for 48 h. In Exp. 1 steers were randomly assigned to treatments. In Exp. 2 steers were blocked by age (OLD or YOUNG) and assigned to treatments. Fecal and urinary excretions accounted for 65 and 38% of the total weight lost in Exp. 1 and 2, respectively. Fasting plus transit did not consistently increase the amount of weight lost compared with fasting alone but increased (P less than .01) plasma glucose concentrations. Injection of ACTH before either fasting alone or fasting plus transit increased (P less than .05) the amount of weight lost as feces. Steers in the OLD group lost more weight during transit and fasting but regained the lost weight faster (P less than .01) during the recovery period than did steers in the YOUNG group. Injecting YOUNG steers with ACTH before fasting alone or fasting plus transit increased plasma fibrinogen (P less than .10) and serum glucose (P less than .05) concentrations more than ACTH injections in OLD steers. Although fasting and transit elicit mobilization of body nutrients and resulted in a loss of BW, these effects were quickly reversed during the poststress period.

Adrenocorticotropic Hormone↗

Enhanced plasma and target tissue availabilities of albendazole and albendazole sulphoxide in fasted calves: evaluation of different fasting intervals.

The influence of different pre- and post-treatment fasting periods on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide metabolite (ABZSO) in cattle was investigated. The effect of fasting on the distribution of ABZ and ABZSO to different target tissues/fluids was also characterised. In Experiment I, 35 parasite-free Holstein calves were divided into seven groups according to the following feeding conditions and treated intraruminally with ABZ (10 mg/kg): control group (fed ad libitum), 24 h fasting either prior to (24 h pre-) or post (24 h post-) treatment, 24 h fasting with either 6 (6 h pre + 18 h post) or 12 h (12 h pre + 12 h post-) of feed restriction prior to treatment, 12 h fasting either prior to (12 h pre-) or post (12 h post) treatment. In Experiment II, calves from the same pool of animals were subjected to a 24 h fasting period prior to the same ABZ treatment and killed (two animals) at either 24, 36 or 48 h post-administration to obtain samples of abomasal/intestinal mucosa and fluid contents, bile and lungs. Plasma (Experiment I) and tissues/fluids (Experiment II) samples were analysed by HPLC. All the fasting periods investigated induced marked changes to the plasma availability and disposition kinetics of the ABZSO metabolite. Enhanced plasma availability between 37 and 118%, delayed peak concentrations and extended mean residence times for ABZSO were observed in fasted compared to fed calves. The changes in plasma kinetics, reflecting an altered quantitative gastrointestinal absorption, were reflected in increased availability of ABZ and ABZSO in the target tissues/fluids of fasted calves. The availabilities of ABZ and ABZSO in the gastrointestinal mucosa and fluids in fasted calves were markedly greater than in those fed ad libitum.

Albendazole↗

Different pharmacokinetics of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-(3-14C)dithiazocine-4-carboxyli c acid between the fasting and non-fasting rat: role of intestinal microorganisms.

1. We report differences in the pharmacokinetics of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-(3-14C)dithiazocine-4-carb oxylic acid (14C-SA3443) between the normal fasting and non-fasting rat, especially in the blood concentration-time curves and respiratory excretion. Exhalation of 14CO2 was an important route of elimination and accounted for 21.2% of the dose in the non-fasting rat but only 3.7% in fasting animals. 2. In the intestinal microorganism-compromised rat, we found little differences in the pharmacokinetics of 14C-SA3443 between fasting and non-fasting states. No respiratory excretion was observed in the intestinal microorganism-compromised animal. 3. In the reaction mixture of 14C-SA3443 with the cecal contents of rat, 14C-acetic acid and 14C-butyric acid were detected and 14CO2 barely detected. 4. The amounts of 14C-acetic acid and 14C-butyric acid in the reaction mixture of 14C-SA3443 with non-fasting rat cecal contents were more than those with fasting rat cecal contents. 5. We concluded that the reason for the different pharmacokinetics of 14C-SA3443 between the fasting and non-fasting rat was the differences in participation of the metabolism of 14C-SA3443 by intestinal microorganisms.

Adjuvants, Immunologic↗

Is long-distance bird flight equivalent to a high-energy fast? Body composition changes in freely migrating and captive fasting great knots.

We studied changes in body composition in great knots, Calidris tenuirostris, before and after a migratory flight of 5,400 km from northwest Australia to eastern China. We also took premigratory birds into captivity and fasted them down to their equivalent arrival mass after migration to compare organ changes and nutrient use in a low-energy-turnover fast with a high-energy-turnover fast (migratory flight). Migrated birds were as economical as any fasting animal measured yet at conserving protein: their estimated relative protein contribution (RPC) to the energy used was 4.0%. Fasted birds had an estimated RPC of 6.8% and, consequently, a much lower lean mass and higher fat content for an equivalent body mass than migrated birds. Lean tissue was catabolized from most organs in both groups, except the brain. Furthermore, a principal components biplot showed that individuals were grouped primarily on the basis of overall organ fat or lean tissue content rather than by the size of specific organs. This indicates that organ changes during migratory flight are similar to those of a low-energy fast, although the length of the fast in this study probably accentuated organ reductions in some functional groups. Whether the metabolic characteristics of a flying migratory fast follow the three-phase model described in many inactive fasting animals is unclear. We have some evidence for skeletal fat being catabolized without phase 3 of a fast having been reached.

Analysis of Variance↗

Ketone-glucose interaction in fed, fasted, and fasted-infected sheep.

Ketosis following starvation was suppressed by hindlimb infection in seven fasted sheep. Glucose production determined following the primed constant infusion of [6-3H(N)]glucose was elevated in the fasted-infected animals (9.50 +/- 1.11 mmol X kg-1 X min-1 (mean +/- SE) versus fasted controls (5.56 +/- 2.2). To determine if the ketonemia following sepsis contributed to the increased glucogenesis associated with catabolic disorder, glucose production and arterial substrates were measured before and after infusion of sodium-DL-beta-hydroxybutyrate (beta-OHB, 20 mumol X kg-1 X min-1) in fed, fasted, and fasted-infected animals. Following 3 h of beta-OHB infusion in the awake conditioned animals, beta-OHB and acetoacetate blood concentrations more than doubled. With infusion, blood glucose and alanine concentrations decreased in the fed and fasted sheep but not in the fasted-infected group. Glucose production fell significantly from 10.11 +/- 1.33 to 8.44 +/- 1.05 in the fed animals and from 5.05 +/- 0.28 to 4.11 +/- 0.33 in the fasted group. Glucose production was unaffected by beta-OHB infusion in the fasted-infected animals (9.50 +/- 1.83 vs. 9.11 +/- 1.44). The accelerated rate of glucose production in sheep following infection is not a consequence of the hypoketonemic state associated with sepsis.

Acidosis↗

Effect of fasting and fasting and refeeding on hepatic and renal gluconeogenic enzymes in the chicken.

The effect of fasting and fasting and refeeding on hepatic and renal gluconeogenic enzyme activities were studied in six-week-old chickens (Gallus domesticus: New Hampshire male x Columbian female). Hepatic pyruvate carboxylase appeared not to be affected by fasting, but the renal enzyme activity increased in four-day fasted chickens. The hepatic mitochondrial and cytosolic phosphoenolpyruvate carboxykinases were essentially not affected by fasting. The renal mitochondrial phosphoenolpyruvate carboxykinase showed a slight increase in activity only after a four-day fast, but the cytosolic enzyme activity increased markedly already after a two-day fast. Also the activities of the hepatic and renal fructose-1,6-diphosphatase and glucose-6-phosphatase increased markedly on fasting. Refeeding for four days after a four-day fast returned these enzyme activities to near control values.

Animals↗

The dietary composition of pre-fast meals and its effect on 24 hour food and water fasting.

BACKGROUND: Fasting is required by the Jewish and Islamic religions, and may sometimes be necessary for non-religious reasons as well. Very little empiric data are available on the effect of 24 hours of food and water deprivation. OBJECTIVES: To compare the effects of the dietary composition of different pre-fast meals on subjective discomfort and various other parameters of a 24 hour food and water fast. METHODS: Thirteen volunteers of both genders participated in a non-randomized crossover study. Each consumed three different equicaloric pre-fast meals in which the main source of calories was protein (49% of calories), carbohydrate (86%), or fat (69%). Weight, heart rate, blood pressure, blood and urine were tested before and after 24 hours of fasting, and the subjective evaluations of the discomfort during the three fasts were compared. RESULTS: After the protein-rich meal greater discomfort and more side effects were reported. Weight and blood pressure decreased at the end of the fasts that followed each of the three meals; heart rate increased after the high fat and carbohydrate meals but not after the protein meal. The main laboratory findings were a 40% increase in blood urea nitrogen and higher urine osmolarity after the protein-rich meal than after the other meals. CONCLUSION: A protein-poor pre-fast meal is likely to be followed by easier fasting.

Adult↗

Synchronous firing of inhibitory interneurons results in saturation of fast GABA(A) IPSC magnitude but not saturation of fast inhibitory efficacy in rat neocortical pyramidal cells.

The kinetic properties of evoked fast inhibitory postsynaptic currents were examined to elucidate factors underlying the limit on the magnitude of fast inhibition in neocortex. Using whole-cell voltage-clamp recordings from layer V pyramidal neurons in slices of rat somatosensory cortex, fast gamma-aminobutyric acid-A (GABA[A])ergic inhibitory postsynaptic currents were selectively recorded by holding cells at potentials equal to excitatory postsynaptic current reversal (approximately 0 mV). As stimulus intensity was increased, the magnitude and duration of the fast inhibitory postsynaptic current increased. Over the range of stimuli applied (2-10 V), fast GABA(A)-mediated inhibitory postsynaptic currents reached a maximum peak conductance of 25.9 +/- 4.2 nS (range 10.5-41.2 nS) at intensities approximately 2-times threshold. As stimulus intensities were increased beyond this point of maximal conductance, the time constant of current decay increased as function of stimulus strength, while rise time remained unaffected. Exposure to nominally magnesium-free solutions did not affect maximal peak conductances of fast inhibitory postsynaptic currents, but did cause an increase in the time constants of current decay by 66.3 +/- 23.6%, resulting in an 85.6 +/- 24.6% increase in the total charge flux carried by single inhibitory postsynaptic currents. This effect may be due to prolonged activation of postsynaptic GABA(A) receptors by excess GABA released in response to increased excitation. Exposure to the GABA uptake blocker, nipecotic acid, similarly prolonged current decay without affecting the maximal peak conductance. Our findings suggest that the limit on recruitment of evoked fast inhibition in neocortical layer V pyramidal cells arises from the saturation of postsynaptic GABA(A) receptors. However, while there is a limit to the peak fast inhibitory postsynaptic conductance which can be recruited with increasing excitation, inhibitory strength may still be modulated by increasing charge flux through the prolongation of fast inhibition.

Animals↗