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Biomedical subjects

B Lancaster

Publications and source records attributed to B Lancaster.

At least 19 recordsLinked to original sources
PubMed2001

Interaction between synaptic excitation and slow afterhyperpolarization current in rat hippocampal pyramidal cells.

1. Whole cell recordings from CA1 pyramidal cells were performed to investigate the interaction between excitatory postsynaptic potentials (EPSPs) or currents (EPSCs), and the slow Ca(2+)-dependent K(+) current, I(sAHP). Blockers of the slow afterhyperpolarization (sAHP) such as isoprenaline (ISO) or noradrenaline (NA) reduced the hyperpolarization that followed a short train of EPSPs, and slowed the decay of summated EPSPs or EPSCs. 2. ISO/NA action on synaptic responses was observed in the absence of action potentials, but was curtailed by Ca(2+) chelation (10 mM EGTA in the electrode) and was not observed with a caesium-based recording solution. This suggests the involvement of an ISO/NA-sensitive Ca(2+)-dependent K(+) current without a requirement for regenerative spiking. 3. An ISO/NA-sensitive sAHP was observed following both NMDA and non-NMDA receptor-mediated EPSP trains in nominally zero Mg(2+) medium. Isoprenaline sensitivity was blocked by hyperpolarization during EPSPs or by isradipine, suggesting a requirement for voltage-dependent Ca(2+) influx during EPSPs. The data indicate that bursts of EPSPs can activate voltage-gated Ca(2+) channels, which trigger I(sAHP) during synaptic responses. 4. A decrease in EPSP temporal summation occurred during both spike-evoked sAHPs and persistent activation of sAHP conductance following internal dialysis with diazo-2 (2 mM). At constant membrane potential, diazo-2 caused a decrease in membrane time constant and input resistance and accelerated the rate of EPSP decay. Photolysis of diazo-2 or application of NA reduced the resting sAHP conductance, causing an increased membrane time constant and input resistance in association with an increase in EPSP half-width. 5. These results indicate that short bursts of EPSPs can activate a Ca(2+)-dependent K(+) current resembling I(sAHP), and that activation of this current reduces the postsynaptic response to high-frequency synaptic input. The findings imply that modulation of I(sAHP) can regulate synaptic efficacy and may influence the threshold for tetanus-induced synaptic plasticity.

Adrenergic alpha-Agonists↗
PubMed2000

Novel action of BAPTA series chelators on intrinsic K+ currents in rat hippocampal neurones.

1. Whole-cell recordings were made from rat CA1 neurones in brain slices. When electrodes contained diazo-2 (2 mM) or dibromo BAPTA (1 mM) a large steady-state outward current (hundreds of picoamps) developed within 5 min of breakthrough at a VH of -60 mV. BAPTA itself (1 mM) caused qualitatively similar but smaller effects. 2. The outward current was accompanied by increased conductance with a null potential close to the calculated K+ equilibrium potential (EK) of -110 mV. Development of outward current occurred concurrently with progressive loss of slow AHP tail current (IsAHP) evoked by brief depolarizations. The peak latency of IsAHP increased during the onset of chelator action. 3. The persistent outward current was reversibly inhibited by noradrenaline (10 microM) or isoprenaline (2-5 microM), and completely prevented by 8-bromoadenosine 3',5' cyclic monophosphate (8-Br cAMP; 100 microM) or QX-314 (10 mM) in recording electrodes. After development of outward current, diazo-2 photolysis caused inward current and decreased conductance. Both flash- and noradrenergic-sensitive responses were inwardly rectifying outward currents with null potentials close to EK. 4. The outward current induced by dibromo BAPTA was not blocked by internal EGTA (10 mM). However, experiments incorporating Ca2+ influx or Ca2+ loading of the buffer indicate that Ca2+ facilitated the outward current. 5. The outward currents induced by dibromo BAPTA or diazo-2 were not associated with significant changes in resting [Ca2+]i. Regions of the cell contributing to the outward current were deduced from measurements of fura-2 diffusion. These were compared with regions of [Ca2+]i elevation during IsAHP. 6. These results are consistent with the hypothesis that the BAPTA series Ca2+ buffers can activate those Ca2+-activated K+ channels that underlie the slow AHP, without the predicted elevation of bulk [Ca2+]i. Therefore these results cannot be interpreted solely in terms of Ca2+ concentration changes, although the observations illustrate a novel, investigative role for these compounds in the study of Ca2+-dependent processes.

Adrenergic alpha-Agonists↗
PubMed2000

Health promotion in the city: a structured review of the literature on interventions to prevent heart disease, substance abuse, violence and HIV infection in US metropolitan areas, 1980-1995.

To achieve its national public health goals, the US must improve the health of low-income urban populations. To contribute to this process, this study reviewed published reports of health promotion interventions designed to prevent heart disease, HIV infection, substance abuse, and violence in US cities. The study's objectives were to describe the target populations, settings, and program characteristics of these interventions and to assess the extent to which these programs followed accepted principles for health promotion. Investigators searched five computerized databases and references of selected articles for articles published in peer-reviewed journals between 1980 and 1995. Selected articles listed as a main goal primary prevention of one of four index conditions; were carried out within a US city; included sufficient information to characterize the intervention; and organized at least 25% of its activities within a community setting. In general, programs reached a diverse population of low-income city residents in a variety of settings, employed multiple strategies, and recognized at least some of the principles of effective health promotion. Most programs reported a systematic evaluation. However, many programs did not involve participants in planning, intervene to change underlying social causes, last more than a year, or tailor for the subpopulations they targeted, limiting their potential effectiveness. Few programs addressed the unique characteristics of urban communities.

HIV Infections↗
PubMed1998

A peptide activator of endogenous tyrosine kinase enhances synaptic currents mediated by NMDA receptors.

N-methyl-D-aspartic acid (NMDA) receptor currents in cultured cells or expression systems are increased by the addition of purified tyrosine kinases. However, there is no direct demonstration of this effect at NMDA receptors in intact synapses of rat brain slices. Transmitters which might be used to activate tyrosine kinases in situ are unlikely to have a sufficiently selective action to allow a clear interpretation of their effects. Therefore, we used a phosphotyrosine-containing decapeptide which can be included in recording electrodes to activate postsynaptic src-family tyrosine kinases. This peptide enhanced NMDA responses in dissociated hippocampal CA1 neurons. These effects were not reproduced by a non-phosphorylated peptide or a scrambled-sequence phosphopeptide. The enhancement of NMDA responses was blocked by a tyrosine kinase inhibitor. In brain slices the phosphopeptide, but not control peptide, increased NMDA receptor-mediated synaptic current indicating that endogenous tyrosine kinase can upregulate the response of NMDA receptors at glutamatergic synapses in the hippocampus.

Animals↗
PubMed1998

Age, ethnicity, and comorbidity in a national sample of hospitalized alcohol-dependent women veterans.

OBJECTIVE: Treatment patterns in a national sample of hospitalized women veterans diagnosed with alcohol dependence were identified with the goal of improving health services to women veterans with alcohol-related disorders. METHODS: Information from VA's patient treatment file for fiscal year 1993 was used to identify 854 women veterans diagnosed with alcohol dependence. Of that group, 546 received a primary diagnosis of alcohol dependence, and 308 received a secondary diagnosis of alcohol dependence after they sought treatment for other health problems. Chi square tests and multivariate logistic regression analyses were used to examine relationships between the sociodemographic profiles of these women and the types of services they received. RESULTS: The study population's largest age group (49 percent) was 30 to 39 years old. Fifty-two percent of the women were divorced or separated, and 62 percent were Caucasian. The overwhelming majority of comorbid diagnoses were of psychiatric disorders. Overall, only 47 percent of the 854 patients received formal treatment for their alcohol disorder, and only 34 percent completed alcohol treatment. Women over age 60 were significantly less likely than women in other age groups to enter or complete formal treatment. Native-American women were significantly more likely than Caucasians or African Americans to receive formal alcohol treatment services. CONCLUSIONS: The results indicate a need for targeting interventions more effectively in certain groups of women veterans diagnosed with alcoholism. Low completion rates also suggest a need for greater incentives for patients to complete treatment programs.

Adult↗
PubMed1998

Disease prevention and health promotion in urban areas: CDC's perspective.

The mission of the Centers for Disease Control and Prevention (CDC) is to prevent disease, injury, and premature death and to promote quality of life. This mission applies to all Americans, especially to the poor and underserved. As so many people who are impoverished live in America's urban areas, the CDC has a unique and specific interest in the health problems of our urban population. The CDC has established five priorities: (1) strengthen essential public health services, (2) enrich capacity to respond to urgent threats to health, (3) develop a nationwide prevention network and program, (4) promote women's health, and (5) invest in our nation's youth. Each of these priorities will contribute to improving the health of people living in urban areas. The CDC has recently undertaken numerous initiatives to address health promotion and disease prevention issues in the urban setting. Future directions for the CDC lie in better understanding the role of socioeconomic and cultural factors in promoting health and how resources within urban areas can be used to promote health. The CDC needs to explore potential relationships with various types of partners. Solving urban health problems requires actions from many federal agencies as well as from state and local organizations.

Adolescent↗
PubMed1996

Tyrosine kinase is required for long-term depression in the cerebellum.

Long-term depression (LTD) at the parallel fiber-Purkinje cell synapse in the cerebellum is a well-known example of synaptic plasticity. Although LTD is thought to reflect an enduring loss of postsynaptic AMPA receptor sensitivity, the underlying mechanisms are unclear. Protein-tyrosine kinases (PTKs) are able to modulate ionotropic receptor function and are enriched in Purkinje cells. Using intracellular recording from Purkinje cells, it is shown that two structurally and mechanistically distinct PTK inhibitors, lavendustin A and herbimycin A, block LTD induced by pairing parallel fiber stimulation with postsynaptic Ca2+ spiking. Intracellular application of the protein kinase C (PKC) activator, (-)-indolactam V, consistently depressed parallel fiber-Purkinje cells EPSPs and occluded pairing-induced LTD. Herbimycin A nullified the run-down produced by (-)-indolactam V. These data suggest that PTKs are necessary for LTD at the parallel fiber-Purkinje cell synapse and that PKC-induced synaptic depression requires PTK activity.

Animals↗
PubMed1996

Laparoscopic drainage of right subphrenic abscess: report of one case.

Laparoscopic surgery has proven to be a very useful technique. Subphrenic abscess, although a rare entity, occurs in the majority of the cases in association with gastroduodenal and biliary disease, appendicitis, or following abdominal surgery. We present the case of a 45-year-old male with a right subphrenic abscess that was successfully treated by laparoscopy. Laparoscopic drainage of subphrenic abscess should be considered as an alternative modern option when dealing with this problem.

Combined Modality Therapy↗
PubMed1995

Interaction of the antiepileptic drug lamotrigine with recombinant rat brain type IIA Na+ channels and with native Na+ channels in rat hippocampal neurones.

Actions of the new antiepileptic drug lamotrigine (LTG, Lamictal) were characterised using recombinant rat brain type IIA Na+ channels expressed in Chinese hamster ovary (CHO) cells and native Na+ channels in rat hippocampal pyramidal neurones, using whole-cell recording and intracellular recording techniques. In CHO cells, LTG caused a tonic inhibition of Na+ currents in a concentration-dependent and voltage-dependent manner. The half-maximal inhibitory concentration (IC50) of approximately 500 microM was obtained at a holding potential (Vh) of -90 mV compared with an IC50 of 100 microM at a Vh of -60 mV. LTG (50 microM) caused a 10-mV negative shift in the slow, steady-state inactivation curve and delayed considerably the recovery from inactivation, but had no significant effects on the voltage dependence of activation or fast inactivation, suggesting that LTG acts mainly on the slow inactivated state. The affinity for the inactivated channels was estimated at 12 microM. The tonic inhibition was augmented by a use-dependent action in which a further inhibition by the drug developed during rapid repetitive stimulation using a train of 20-ms duration pulses (11 Hz). These results were consistent with the drug action being on firing properties of pyramidal neurones. Only in those epilepti-form bursts which caused cumulative inactivation of Na+ spikes did LTG produce a potent inhibition. Our data suggest that the inactivated channel is a primary target for LTG action at therapeutic concentrations.

Action Potentials↗
PubMed1994

Photolytic manipulation of Ca2+ and the time course of slow, Ca(2+)-activated K+ current in rat hippocampal neurones.

1. Experiments were performed on hippocampal CA1 pyramidal cells to investigate the time course of a slow, Ca(2+)-activated K+ current that follows a burst of action potentials. At a temperature of 27-30 degrees C, this current rises to a peak 200-400 ms following the cessation of Ca2+ entry before decaying to baseline in 4-8s. 2. Intracellular recordings were made using electrodes containing the photolabile calcium buffers nitr-5 or DM-nitrophen loaded appropriately with Ca2+. Under these conditions, photolysis of the compound using an ultraviolet flashlamp caused an instantanous increase in cytoplasmic Ca2+ throughout the cell. The response to flash photolysis was a membrane hyperpolarization with an onset limited by the membrane time constant. Multiple (up to twenty) flash responses could be generated. 3. The postspike slow after-hyperpolarization (AHP) and flash-induced hyperpolarizations showed a common sensitivity to the beta-adrenergic receptor agonist isoprenaline. 4. Following a burst of spikes, the current underlying an AHP in progress could be terminated or reduced by photolysis-induced production of calcium buffer from diazo-4 within the cell. This action was rapid (within the setting time of the flash artifact, i.e. < 10 ms) despite the fact that the manipulation occurred 400-500 ms following the end of Ca2+ entry. 5. Partial block of the slow AHP by buffer production was accompanied by an increase in the time to peak of the event. 6. The time to peak of the slow AHP could also be manipulated by experiments which altered the spatial distribution of Ca2+ entry, such as production of calcium spikes or dendritic depolarization by glutamate in the presence of tetrodotoxin. 7. The Ca(2+)-dependent K+ current responsible for the slow AHP responds immediately to increase or decreases in cytoplasmic Ca2+. It seems likely, therefore, that the slow AHP is controlled solely by changes in free Ca2+ and that the time course is governed by the redistribution of cytoplasmic Ca2+ following activity-induced entry through voltage- or receptor-operated channels.

Acetates↗
PubMed1994

Drainage of hepatic amebic abscess successfully treated by laparoscopy.

A case of hepatic amebic abscess is presented that was treated successfully by laparoscopy. The patient was fully worked up, including computed tomography (CT) scan, video-colonoscopy, and blood profiles. The laparoscopic surgical technique is fully discussed and proved to be a very useful tool in the management of this problem, obviating the need for a formal laparotomy and its potential complications.

Aged↗
PubMed1992

Temporal limits on the rise in postsynaptic calcium required for the induction of long-term potentiation.

The induction of long-term potentiation (LTP) in hippocampal CA1 pyramidal cells requires a rise in postsynaptic intracellular Ca2+ concentration ([Ca2+]i). To determine the time for which Ca2+ must remain elevated to induce LTP, the photolabile Ca2+ buffer diazo-4 was used to limit the duration of the rise in postsynaptic [Ca2+]i following a tetanus. The affinity of diazo-4 for Ca2+ increases approximately 1600-fold upon flash photolysis, permitting almost instantaneous buffering of [Ca2+]i without disturbing resting [Ca2+]i prior to the flash. Photolysis of diazo-4 1 s following the start of the tetanus blocked LTP, while delaying photolysis for more than 2 s had no discernible effect on LTP. Photolyzing diazo-4 at intermediate delays (1.5-2 s) or reducing photolysis of diazo-4 often resulted in short-term potentiation (STP). These results indicate that a tetanus-induced rise in postsynaptic [Ca2+]i lasting at most 2-2.5 s is sufficient to generate LTP. Smaller increases or shorter duration rises in [Ca2+]i may result in STP.

Action Potentials↗
PubMed1991

Calcium activates two types of potassium channels in rat hippocampal neurons in culture.

Several calcium-dependent potassium currents can contribute to the electrophysiological properties of neurons. In hippocampal pyramidal cells, 2 afterhyperpolarizations (AHPs) are mediated by different calcium-activated potassium currents. First, a rapidly activated current contributes to action-potential repolarization and the fast AHP following individual action potentials. In addition, a slowly developing current underlies the slow AHP, which occurs after a burst of action potentials and contributes substantially to the spike-frequency accommodation observed in these cells during a prolonged depolarizing current pulse. In order to investigate the single Ca2(+)-dependent channels that might underlie these currents, we performed patch-clamp experiments on hippocampal neurons in primary culture. When excised inside-out patches were exposed to 1 microM Ca2+, 2 types of channel activity were observed. In symmetrical bathing solutions containing 140 mM K+, the channels had conductances of 19 pS and 220 pS, and both were permeable mainly to potassium ions. The properties of these 2 channels differed in a number of ways. At negative membrane potentials, the small-conductance channels were more sensitive to Ca2+ than the large channels. At positive potentials, the small-conductance channels displayed a flickery block by Mg2+ ions on the cytoplasmic face of the membrane. Low concentrations of tetraethylammonium (TEA) on the extracellular face of the membrane specifically caused an apparent reduction of the large-channel conductance. The properties of the large- and small-conductance channels are in accord with those of the fast and slow AHP, respectively.

Animals↗
PubMed1987

Potassium currents evoked by brief depolarizations in bull-frog sympathetic ganglion cells.

1. Sympathetic neurones of the bull-frog Rana catesbeiana were subjected to a two-electrode voltage-clamp technique in order to investigate the K+ currents which can be elicited by action potentials or similar brief depolarizations. 2. Four separate K+ currents were observed (IC, IK, IAHP and IM). These could be separated on the basis of voltage sensitivity, Ca2+ dependence and deactivation kinetics. 3. Two of these currents, which were clearly activated by an action potential, were Ca2+ dependent. A voltage- and TEA (tetraethylammonium)-sensitive K+ current, IC, was activated within the first 1-2 ms of a depolarizing command. This current decayed on average with a time constant of 2.4 ms at -40 mV. The maximal conductance was outside the range which could be adequately voltage clamped but, as much as 2 muS could be activated by brief (2-3 ms) commands. Activation of IC during an action potential accounts for the Ca2+ dependence of the repolarization. IC did not exhibit a transient component. 4. A second Ca2+-dependent K+ current, IAHP, was also activated after as little as 1 ms depolarization but was not voltage sensitive and was much less sensitive to TEA. The current decayed with a time constant of around 150 ms at -40 mV. The maximal conductance was about 30 nS. 5. The voltage-sensitive delayed rectifying current, IK, made a contribution to the total K+ conductance of the cell similar to IC in magnitude; however, the current is not activated within the normal voltage range or time course of an action potential. The current decayed on average with a time constant of 21 ms at -40 mV. 6. IM, a muscarine- and voltage-sensitive current, is not activated to any significant degree by a single action potential. The data further imply that the rate of opening of the ion channels mediating IM is less voltage sensitive than the rate of closing. 7. Large changes in the K+ reversal potential occur following depolarizing commands which evoke large K+ currents. This is attributed to K+ accumulation within a restricted extracellular space. Extracellular K+ may double or even triple during a single action potential.

Action Potentials↗
PubMed1987

Properties of two calcium-activated hyperpolarizations in rat hippocampal neurones.

1. Intracellular recording from hippocampal CA1 pyramidal cells in the slice preparation was used to analyse the pharmacological sensitivity of action potential repolarization and the hyperpolarizations that follow the action potential. The Ca2+-activated after-hyperpolarizations (a.h.p.s) could be divided into a fast a.h.p. with a time course of milliseconds, and a slow a.h.p. which lasted for a few seconds at a temperature of 30 degrees C. 2. The repolarization of the action potential is sensitive to the Ca2+ channel blocker Cd2+. This effect is simultaneous with a block of the fast a.h.p. which follows immediately upon the repolarization of the action potential. The slow a.h.p. was also blocked by Cd2+. 3. Low concentrations of the K+ channel blocker, tetraethylammonium (TEA; 200-500 microM), block the fast a.h.p. and slow down action potential repolarization. The slow a.h.p. was not affected by low concentrations of TEA. 4. The action potential repolarization and the fast a.h.p. are also reversibly sensitive to charybdotoxin. This agent had no effect on the slow a.h.p. 5. When EGTA or BAPTA were added to the normal recording electrolyte (KMeSO4), the generation of slow a.h.p.s was prevented. In addition, cells impaled with BAPTA-containing electrodes displayed broader action potentials and much reduced fast a.h.p.s compared to recordings made with electrodes containing KMeSO4 alone or with EGTA. 6. The slow a.h.p. can be eliminated by noradrenaline, 8-bromocyclic AMP or carbachol. Under these conditions there are no effects on the fast a.h.p. or on action potential duration. 7. Block of the fast a.h.p. with TEA or CTX (charybdotoxin) is associated with an increased frequency of the first few action potentials during a depolarization. This is a quite distinct effect from the greatly increased number of action potentials which results from block of the slow a.h.p. 8. The results support a conclusion that the fast a.h.p. is generated by the TEA- and voltage-sensitive Ca2+-activated K+ current, IC. This current is involved in spike repolarization and turns off upon the return to resting potential. Thus block of IC has no effect on the slow a.h.p. which is caused by a separate membrane current.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Voltage clamp analysis of cholinergic action in the hippocampus.

A slow muscarinic EPSP, accompanied by an increase in membrane input resistance, can be elicited in hippocampal CA1 pyramidal cells in vitro by electrical stimulation of cholinergic afferents in the slice preparation. Associated with the slow EPSP is a blockade of calcium-activated potassium afterhyperpolarizations (AHPs) (Cole and Nicoll, 1984a). In this study a single-electrode voltage clamp was used to examine the currents affected by activation of muscarinic receptors, using either bath application of carbachol or electrical stimulation of the cholinergic afferents. The 3 main findings of this study are that (1) of the 2 calcium-activated potassium currents (termed IAHP and IC) in hippocampal pyramidal cells, only IAHP is sensitive to carbachol; (2) IAHP is approximately 10-fold more sensitive to carbachol than is another muscarine-sensitive current, IM; and (3) neither blockade of IAHP nor of IM can account for the production of the slow EPSP. Rather, the slow EPSP appears to be generated by the blockade of a nonvoltage-dependent, resting potassium current. We propose that the muscarinic blockade of IAHP, which largely accounts for spike frequency adaptation, is primarily involved in enhancing action potential discharge to depolarizing stimuli, while the slow EPSP acts directly to cause action potential discharge.

Acetylcholine↗