Biomedical subjects

M C Wallace

Publications and source records attributed to M C Wallace.

At least 19 recordsLinked to original sources

PubMed1999

Decreased hippocampal expression, but not functionality, of GABA(B) receptors after transient cerebral ischemia in rats.

We have examined the effects of transient global ischemia on both the gene expression levels and the functionality of GABA(B) receptors in rat brain, using antisense in situ hybridization and electrophysiological evaluations. At the level of gene expression, no significant change in GABA(B) receptor expression was observed in any hippocampal subfield at either 6 or 12 h after challenge. At 24 h postchallenge, however, a significant decrease in GABA(B) receptor expression was observed in both the CA1 and CA3 subfields, whereas no change was observed in the dentate granule cell layer. Although expression in both the vulnerable CA1 and less vulnerable CA3 subfields was diminished at this time postchallenge, there was no significant difference in the degree of the diminished expression between these subfields. At the functional level, the dose-dependent ability of baclofen (1-100 microM) to inhibit an evoked excitatory postsynaptic potential (f-EPSP) in the CA1 subfield was evaluated at 24 h postischemia, in comparison with the dose-response observed in sham-operated subjects. No significant differences were observed in the efficacy of GABA(B) receptor-mediated inhibition of the elicited f-EPSP at any of the baclofen concentrations examined. These data demonstrate that although the mRNA expression levels for the GABA(B) receptor are diminished in both vulnerable and less vulnerable neurons of Ammon's horn at 24 h following transient global ischemia, the functionality of the GABA(B) receptor system is maintained at this time postchallenge.

Animals↗

PubMed1998

Decreased expression and functionality of NMDA receptor complexes persist in the CA1, but not in the dentate gyrus after transient cerebral ischemia.

The authors investigated the gene expression of the NR2A and NR2B subunits of N-methyl-D-aspartate (NMDA) receptor and the functional electrophysiologic activity of NMDA receptor complexes in the vulnerable CA1 and less vulnerable dentate gyrus subfields of the rat hippocampus at different times after transient cerebral ischemia. Decreased expression for both subtypes was observed in both the CA1 subfield and dentate granule cell layer at early times after challenge; however, the decreased expression in the dentate granule cell layer was reversible because mRNA levels for both the NR2A and NR2B subtypes recovered to, or surpassed, sham-operated mRNA levels by 3 days postchallenge. No recovery of expression for either subtype was observed in the CA1 subfield. The functional activity of NMDA receptor complexes, as assessed by slow field excitatory postsynaptic potentiations (slow f-EPSP) in CA1 pyramidal neurons, was maintained at 6 hours postchallenge; however, this activity was diminished greatly by 24 hours postchallenge, and absent at 7 days postchallenge. A similar pattern was observed for the non-NMDA receptor-mediated fast f-EPSP. In dentate granule neurons, however, no significant change in NMDA receptor-mediated slow f-EPSP from sham control was observed at any time after insult. The non-NMDA receptor-generated fast f-EPSPs also were maintained at all times postinsult in the dentate gyrus. These results illustrate that the activity of NMDA receptors remains functional in dentate granule neurons, but not in the pyramidal neurons of the CA1 subfield, at early and intermediate times after transient cerebral ischemia, and suggest that there is a differential effect of ischemia on the glutamatergic transmission systems in these two hippocampal subfields.

Animals↗

PubMed1998

Acute human histopathology of an intracranial aneurysm treated using Guglielmi detachable coils: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: This case study provided us with the opportunity to explore the histopathological effects of Guglielmi detachable coil (GDC) therapy on the aneurysm orifice and parent vessel-aneurysm neck interface. This type of study is important to the understanding of the mechanisms of obliteration of aneurysms by GDCs. CLINICAL PRESENTATION: The patient presented with a Hunt and Hess Grade III subarachnoid hemorrhage that occurred secondary to the rupture of a small anterior communicating artery aneurysm. INTERVENTION: The aneurysm was successfully coiled without complication, but the patient died 36 hours later. We examined the gross and microscopic pathological findings of this GDC-treated anterior communicating artery aneurysm 36 hours after coiling. A discrete membrane composed of fibrin had formed completely across the aneurysm orifice, excluding the aneurysm sac from the circulation. This membrane was contiguous with the parent vessel. CONCLUSION: This case represents one of the first examples in humans of the formation of a membrane over the aneurysm orifice after GDC therapy. The formation of this membrane, shown to be composed of fibrin, was found at 36 hours after coiling, which is the earliest time frame at which membrane formation has been noted in either humans or animal models. This fibrin membrane may function both as a scaffold for subsequent endothelialization across the aneurysm neck as well as to isolate the aneurysm from the parent circulation, permitting thrombus within the aneurysm sac to mature to an endovascular scar. The factors contributing to the formation of this membrane and its clinical implications are discussed.

Aged↗

PubMed1998

Pediatric intracranial aneurysms.

Pediatric intracranial aneurysms are uncommon. There are several differences between childhood and adult aneurysms, but the evaluation and management of childhood aneurysms is similar to that in adults. This article will review the incidence, pathology, clinical features, management, and expected outcome of childhood aneurysms.

Adolescent↗

PubMed1997

Guidelines for the use of carotid endarterectomy: current recommendations from the Canadian Neurosurgical Society.

OBJECTIVE: To develop guidelines on the suitability of patients for carotid endarterectomy (CEA). OPTIONS: For atherosclerotic carotid stenosis that has resulted in retinal or cerebral ischemia: antiplatelet drugs or CEA. For asymptomatic carotid stenosis: CEA or no surgery. OUTCOMES: Risk of stroke and death. EVIDENCE: Trials comparing CEA with nonsurgical management of carotid stenosis. VALUES: Greatest weight was given to findings that were highly significant both statistically and clinically. BENEFITS, HARMS AND COSTS: Benefit: reduction in the risk of stroke. Major harms: iatrogenic stroke, cardiac complications and death secondary to surgical manipulations of the artery or the systemic stress of surgery. Costs were not considered. RECOMMENDATIONS: CEA is clearly recommended for patients with surgically accessible internal carotid artery (ICA) stenoses equal to or greater than 70% of the more distal, normal ICA lumen diameter, providing: (1) the stenosis is symptomatic, causing transient ischemic attacks or nondisabling stroke (including retinal infarction); (2) there is no worse distal, ipsilateral, carotid distribution arterial disease; (3) the patient is in stable medical condition; and (4) the rates of major surgical complications (stroke and death) among patients of the treating surgeon are less than 6%. Surgery is not recommended for asymptomatic stenoses of less than 60%. Symptomatic stenoses of less than 70% and asymptomatic stenoses of greater than 60% are uncertain indications. For these indications, consideration should be given to (1) patient presentation, age and medical condition; (2) plaque characteristics such as degree of narrowing, the presence of ulceration and any documented worsening of the plaque over time; (3) other cerebral arterial stenoses or occlusions, or cerebral infarcts identified through neuroimaging; and (4) surgical complication rates at the institution. CEA should not be considered for asymptomatic stenoses unless the combined stroke and death rate among patients of the surgeon is less than 3%. VALIDATION: These guidelines generally agree with position statements prepared by other organizations in recent years, and with a January 1995 consensus statement by a group of experts assembled by the American Heart Association.

Canada↗

PubMed1997

Kainic acid-induced generalized seizures alter the regional hippocampal expression of the rat Kv4.2 potassium channel gene.

Potassium channels play a key role in the regulation of membrane excitability. We investigated the gene expression response of the Kv4.2 subtype of potassium channel, in the rat hippocampus, to a brief (5 min) episode of kainic acid-induced seizures. Our results demonstrate that Kv4.2 expression is reduced in the granule cell layer of the dentate gyrus at 3 h post-seizure, while no significant changes in expression are observed in other hippocampal subfields. At 6 h post-challenge, expression in both dentate hilar cells and granule cells is reduced, while no other significant changes are observed. At 24 h post-challenge, expression levels for Kv4.2 in the dentate granule cells have rebounded to levels greater than control, while expression levels are significantly reduced in the CA3 and CA4 subfields. No significant changes in Kv4.2 expression are observed in kainic acid-administered animals that fail to seize, indicating that the changes in gene expression result from seizure activity and not from the direct actions of the administered kainic acid. These results demonstrate that brief kainic acid-induced epileptiform activity promotes alterations in the expression levels for the Kv4.2 subtype of potassium channel gene.

Animals↗

PubMed1997

Kainic acid-induced generalized seizures alter the regional hippocampal expression of the rat m1 and m3 muscarinic acetylcholine receptor genes.

We investigated the gene expression responses using in situ hybridization with radiolabelled riboprobes for the m1 and m3 subtypes of muscarinic cholinergic receptors in the rat hippocampus following a brief (5-min) kainic acid-induced behavioral seizure. The kainic acid was intraperitoneally administered, and the ensuing generalized convulsive seizure terminated with diazepam. Our results demonstrate that the expression of the m1 subtype was significantly reduced in the CA1, CA3 and the dentate granule cells by 3 h after the administration of kainic acid while no significant change was observed in any hippocampal subfield for the m3 subtype. By 6 h post challenge, the m1 subtype was still decreased in all hippocampal subfields examined, while the m3 subtype remained unchanged from vehicle injected control. At 24 h post challenge, both the m1 and m3 subtypes were significantly reduced in the CA1 and CA3 subfields; the expression of the m1 subtype in the dentate granule cells, however, had recovered to levels indistinguishable from vehicle-injected control. These results demonstrate that epileptiform activity induced by kainic acid administration promotes alterations in the expression levels for both the m1 and m3 muscarinic receptor genes, and suggest that the activity of this neuromodulatory system in the hippocampus may be altered through activity-dependent mechanisms at early times following seizures.

Animals↗

PubMed1997

Transient ischemia differentially increases tyrosine phosphorylation of NMDA receptor subunits 2A and 2B.

Activation of the N-methyl-D-aspartate (NMDA) receptor has been implicated in the events leading to ischemia-induced neuronal cell death. Recent studies have indicated that the properties of the NMDA receptor channel may be regulated by tyrosine phosphorylation. We have therefore examined the effects of transient cerebral ischemia on the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B in different regions of the rat brain. Transient (15 min) global ischemia was produced by the four-vessel occlusion procedure. The tyrosine phosphorylation of NR2A and NR2B subunits was examined by immunoprecipitation with anti-tyrosine phosphate antibodies followed by immunoblotting with antibodies specific for NR2A or NR2B, and by immunoprecipitation with subunit-specific antibodies followed by immunoblotting with anti-phosphotyrosine antibodies. Transient ischemia followed by reperfusion induced large (23-29-fold relative to sham-operated controls), rapid (within 15 min of reperfusion), and sustained (for at least 24 h) increases in the tyrosine phosphorylation of NR2A and smaller increases in that of NR2B in the hippocampus. Ischemia-induced tyrosine phosphorylation of NR2 subunits in the hippocampus was higher than that of cortical and striatal NR2 subunits. The enhanced tyrosine phosphorylation of NR2A or NR2B may contribute to alterations in NMDA receptor function or in signaling pathways in the postischemic brain and may be related to pathogenic events leading to neuronal death.

Animals↗

PubMed1997

Transient global ischemia alters NMDA receptor expression in rat hippocampus: correlation with decreased immunoreactive protein levels of the NR2A/2B subunits, and an altered NMDA receptor functionality.

We investigated the gene expression levels, the immunoreactive protein prevalence, and the functional activity of N-methyl-D-aspartate (NMDA) receptor complexes at early times after severe global ischemia challenge in rats. The mRNA expression levels for the NR2A and NR2B subunits of NMDA receptors changed to different degrees within different subregions of the hippocampus after reperfusion with respect to sham-operated control. No significant change in expression was observed in the vulnerable CA1 subfield at or before 6 h after challenge for either receptor subunit, although changes in expression in other hippocampal subfields were observed. At 12 and 24 h after challenge, significant decreases in expression for both subunits were found in the vulnerable CA1 subfield, as well as in other hippocampal regions. At the protein level, a significant decrease in the amount of NR2A/NR2B immunoreactivity in the total hippocampus was observed at both 6 and 24 h after reperfusion compared with sham control. Electrophysiological assessment of single-channel NMDA receptor activity in the CA1 subfield indicates that the main conductance state of NMDA receptor channels is maintained 6 h after challenge, although by 18-24 h after challenge, this main conductance state is rarely observed. The NMDA receptor component of the excitatory postsynaptic field potential was found to be significantly diminished from sham control 24 h after challenge, such that only approximately 10% of the sham response remained, but was not significantly altered from sham control at 6 h after challenge. These results indicate that decreases in the expression levels, the immunoreactive protein prevalence, and that alterations in the functionality of NMDA receptors occur in the hippocampus at early times after severe transient global ischemia.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1997

Transient ischemia induces an early decrease of synaptic transmission in CA1 neurons of rat hippocampus: electrophysiologic study in brain slices.

We examined the functionality of hippocampal CA1 neurons at early times after transient global ischemia, by electrophysiologic recordings in brain slices. Transient ischemia was conducted on rats using the method of 15-minute four-vessel occlusion, and brain slices were obtained from these animals at different times after ischemia. Within 24 hours after insult, CA1 neurons showed no substantial damage as identified by morphologic means, but exhibited dramatic decreases in synaptic activities by 12 hours after insult, which became further decreased at more extended times after recovery. Blocking gamma-aminobutyric acid A (GABAA) receptors with bicuculline produced a reversible augmentation of the diminished synaptic responses in slices prepared from 12-hour postinsult animals, but failed to do so in slices obtained from rats 24 hours after insult. Recorded in whole-cell mode, the minimum depolarizing current required to elicit an action potential was about twofold larger in the ischemic CA1 neurons than in sham controls, suggesting that an elevated spiking threshold exists in these neurons. We suggest that decreases in electrophysiologic activities precede the morphologic deterioration in postischemic CA1 neurons. The early decrease in CA1 synaptic activities may be associated with an imbalance between glutamate-mediated synaptic excitation and GABAA-mediated synaptic inhibition, whereas substantial impairments in synaptic transmission likely take place after prolonged post-ischemic recovery.

Animals↗

PubMed1997

Surgery versus stereotactic radiosurgery for small, operable cerebral arteriovenous malformations: a clinical and cost comparison.

OBJECTIVE: Cerebral arteriovenous malformations (AVMs) may cause stroke and death in young patients. For small AVMs, the major curative treatment options are surgery and stereotactic radiosurgery (SR). Although the initial costs and risks of SR are less, there is a latency to cure and ultimately the success rate is lower than with surgery. Thus, these two treatment modalities were compared with respect to clinical outcomes and associated costs by means of a cost-effectiveness analysis. METHODS: A decision analysis model was developed using Smltree software (J.P. Hollenberg, Roslyn, NY). Probability estimates for cure and complications for both therapies were derived from the literature. Utility values for minor and major stroke were measured in patients with AVMs who were treated at the University of Toronto clinic, using the standard gamble technique. Costs were obtained from several sources, including the case costing systems of several hospitals in Ontario, Canada. RESULTS: Surgery confers a 0.98 quality-adjusted life year (QALY) advantage over SR, at an additional cost of $6937 per patient. Thus, from a societal perspective, the incremental cost-effectiveness ratio is $7100 per QALY for a patient treated surgically. The result is sensitive to only two variables: surgical morbidity and surgical mortality. However, the preferred treatment strategy changes to favor SR only at the extreme high end of the possible range for these variables, when the rate of permanent neurological morbidity resulting from surgery exceeds 12% or the surgical mortality rate exceeds 4%. CONCLUSIONS: In the treatment of small AVMs, surgery confers a large clinical benefit over SR. The reason is that surgery protects the patient from hemorrhage earlier and with greater success than does SR. The associated cost-effectiveness ratio, $7100/QALY, is highly economically attractive. Therefore, surgery achieves important improvements in clinical outcomes and is associated with an excellent ratio of incremental costs per QALY gained.

Adult↗

PubMed1997

Paving the way: stepping stones to evidence-based nursing.

Evidence-based practice is an emerging paradigm in health care. This paper outlines the main features of this paradigm and its potential value to nursing. Evidence-based practice is based on a conceptual framework that examines the extent of evidence available in support of particular clinical practices. The Quality of Evidence Ratings adapted by the National Health and Medical Research Council (NHMRC) from the United States Preventive Services Task Force are discussed, and the strengths and weaknesses of different categories of evidence are highlighted. Potential barriers to implementation of research into practice are identified. The authors suggest that legal, ethical, economic and humane imperatives oblige nursing to develop evidence-based practice as one of several viable contributions to nursing knowledge. Suggestions for analysing current research and for the planning of the direction of future nursing research are made.

Diffusion of Innovation↗

PubMed1997

Quality of life of stroke in younger individuals. Utility assessment in patients with arteriovenous malformations.

BACKGROUND AND PURPOSE: Patients with arteriovenous malformations are younger individuals who are at risk of a stroke or have experienced one. Our objective was to determine these patients' perceptions of quality of life with a stroke by eliciting utility values. METHODS: Utility values were obtained with the standard gamble technique. Utilities are a holistic, quality of life measure between 0 and 1. We evaluated the patients' current health state and written descriptions of major and minor stroke. RESULTS: Thirty-one consecutive outpatients participated. The mean age was 37 years (range, 18 to 57 years). Approximately 65% had suffered a stroke, of which 55% were major. Approximately 61% had a persistent deficit. The mean utilities were 0.45 for major stroke (95% confidence interval [CI], 0.33 to 0.56; range, 0.00 to 1.00), 0.81 for minor stroke (95% CI, 0.75 to 0.88; range, 0.30 to 1.00), and 0.81 for current health (95% CI, 0.73 to 0.89; range, 0.01 to 1.00). Subgroup analyses by demographic and clinical characteristics showed no significant differences. However, in both those patients who had never had a stroke and those who had survived a major stroke, values for the major stroke scenario were clustered at the two extremes. Among those with a current deficit, 79% preferred their own health state to that of the stroke scenario that was similar in severity. CONCLUSIONS: Younger people who have had a stroke or are at risk demonstrate wide variations in their perception of quality of life. Furthermore, patients tend to be more risk averse with their own lives than with theoretical scenarios. We suggest tailoring medical decision making to individual preferences.

Adolescent↗

PubMed1997

Multilevel anterior cervical corpectomy and fibular allograft fusion for cervical myelopathy.

This study was conducted to determine the safety and efficacy of multilevel anterior cervical corpectomy and stabilization using fibular allograft in patients with cervical myelopathy. Thirty-six patients underwent this procedure for cervical myelopathy caused by spondylosis (20 patients), ossified posterior longitudinal ligament (four patients), trauma (one patient), or a combination of lesions (11 patients). The mean age (+/- standard deviation) of the patients was 58 +/- 10 years and 30 of the patients were men. The mean duration of symptoms before surgery was 30 +/- 6 months and 11 patients had undergone previous surgery. Prior to surgery, the mean Nurick grade of the myelopathy was 3.1 +/- 1.4. Seventeen patients also had cervicobrachial pain. Four vertebrae were removed in six patients, three in 19, and two in 11 patients. Instrumentation was used in 15 cases. The operative mortality rate was 3% (one patient) and two patients died 2 months postoperatively. Postoperative complications included early graft displacement requiring reoperation (three patients), transient dysphagia (two patients), cerebrospinal fluid leak treated by lumbar drainage (three patients), myocardial infarction (two patients), and late graft fracture (one patient). One patient developed transient worsening of myelopathy and three developed new, temporary radiculopathies. All patients achieved stable bone union and the mean Nurick grade at an average of 31 +/- 20 months (range 0-79 months) postoperatively was 2.4 +/- 1.6 (p < 0.05, t-test). Cervicobrachial pain improved in 10 (59%) of the 17 patients who had preoperative pain and myelopathy improved at least one grade in 17 patients (47%; p < 0.05). Twenty-six surviving patients (72%) were followed for more than 24 months and stable, osseous union occurred in 97%. These results show that extensive, multilevel anterior decompression and stabilization using fibular allograft can be achieved with a perioperative mortality and major morbidity rate of 22% and with significant improvement in pain and myelopathy.

Aged↗

PubMed1997

Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage.

Despite recent studies of the natural history of cavernous malformations, there remains significant uncertainty concerning hemorrhage rates and the importance of lesion location. Controversy arises over varying definitions of "hemorrhage." What is ultimately important to the patient is the occurrence of a neurological event, which may or may not be associated with radiologically documented hemorrhage, as well as the chance of recovery after such an event. The purpose of this study was to determine the rates of occurrence and sequelae of neurological events in 173 patients referred to our vascular malformation clinic with cavernous malformations. All patient data were entered into a database. The mean age at presentation for the 173 patients was 37.5 years. The lesion location was deep (brainstem, cerebellar nuclei, thalamus, or basal ganglia) in 64 patients (37%) and superficial in 109 (63%). Thirty-one patients (18%) had multiple lesions. Disease presentation was due to seizures in 62 patients (36%), hemorrhage in 44 (25%), focal neurological deficit without documented hemorrhage in 35 (20%), headache alone in 11 (6%), and incidental findings in 21 patients (12%). The results obtained in the 110 patients eligible for follow-up review were used to derive information on the rates of hemorrhage and neurological events. An interval event (neurological deterioration) required both symptoms and signs. The total mean follow-up period was 46 months, the majority (65%) of which was prospective. There were 18 interval events in 427 patient-years of follow-up review, for an overall annual event rate of 4.2%. Location was the most important factor for predicting interval event occurrence, with significantly higher rates for deeply located (10.6%/year) compared with superficially located lesions (0%/year) (p = 0.0001). Of patients suffering a neurological event, only 37% had complete resolution of their deficits. This largely prospective study indicates that deep cavernous malformations carry a worse prognosis than superficial lesions with respect to annual rates of neurological deterioration. The alarming rate of adverse clinical events occurring in patients with deep lesions is punctuated by the fact that less than one-half of them recover fully during long-term follow-up review.

Adult↗

PubMed1997

Spinal epidural arteriovenous fistula with intramedullary reflux. Case report.

A spinal epidural arteriovenous fistula with secondary reflux into the perimedullary veins is a rare entity. The authors present such a case with a discussion of its pathophysiology and treatment. The mechanism for formation of a spinal dural arteriovenous fistula is outlined based on the anatomical substrates in this region.

Aged↗

PubMed1996

Cerebral ischemia alters the regional hippocampal expression of the rat m1 muscarinic acetylcholine receptor gene.

We investigated the dynamics of the gene expression of the m1 subtype of muscarinic cholinergic receptor in the rat hippocampus following transient global ischemia. This receptor represents the dominant phosphoinositide linked muscarinic receptor in the hippocampus, and is recognized to modulate various aspects of neuronal activity in the hippocampus. Our results demonstrate that following severe transient global ischemia, m1 receptor expression is altered in the hippocampus in a time dependent manner. Expression levels declined in the dentate gyrus within 3 h of insult, reached minimal levels by 6 h, and then slowly recover to control levels. Expression levels in the CA1 and CA3 decreased as well, but did not reach minimal levels until 24 h post-insult. By day 3, expression levels in all regions except CA1, where vulnerable neurons began to drop out, had returned to control levels. These results demonstrate that transient alterations in the gene expression levels for the m1 muscarinic receptor occur in all subfields of the hippocampus following transient forebrain ischemia.

Animals↗

PubMed1996

Accumulation and extrusion of permeant Ca2+ chelators in attenuation of synaptic transmission at hippocampal CA1 neurons.

The effects of extracellularly applied membrane-permeant Ca2+ chelators on field excitatory postsynaptic potentials were determined in the hippocampal CA1 region of rat brain slices. Field excitatory postsynaptic potentials in slices perfused with 0.05-50 microM bis-(-O-aminophenoxy)-ethane-N,N,N,N,-tetraacetic acid acetoxymethyl (BAPTA-AM) for 15 min were reversibly attenuated by 10-45% in a concentration-dependent manner. Attenuation occurred earlier at higher concentrations of BAPTA-AM, thus indicating that the rate of accumulation of BAPTA salt was concentration dependent. Antidromically evoked responses and presynaptic volleys were unaffected by BAPTA-AM. Attenuation of the field excitatory postsynaptic potentials by BAPTA-AM was temporarily eliminated by repetitive stimulation at 1 Hz, suggesting saturation of the chelator's Ca(2+)-binding capacity. The amplitude of field excitatory postsynaptic potentials was unaffected by similar applications of 5'5-dinitro-BAPTA-AM, a low Ca(2+)-affinity BAPTA analogue, and EGTA-AM (5 or 50 microM), a chelator with slow Ca(2+)-binding kinetics, suggesting a dependence of the BAPTA-AM effect on fast Ca2+ binding and high Ca2+ affinity. BAPTA-AM concentrations as low as 0.05 microM were effective provided application was prolonged to 40 min. Probenecid (1 mM), an anion transport inhibitor, accelerated the onset and significantly enhanced the BAPTA-mediated synaptic attenuation caused by low concentrations of BAPTA-AM. These data show that even very low extracellular concentrations of BAPTA-AM can profoundly affect synaptic transmission provided that sufficient chelator accumulates presynaptically. The effectiveness of BAPTA-AM can be increased by procedures which inhibit chelator extrusion.

Animals↗