excitotoxic-stimulation-brain-microslices-as-an-vitro-model

Excitotoxic Stimulation of Brain Microslices as an <em>In vitro</em> Model of Stroke

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As ...

The University of Newcastle

In this section eight presenters focus on three distinct aspects of chromaffin cell biology: first, the properties of neuronal nicotinic receptors; second, the shaping of the Ca(2+) signals that underlie chromaffin cell function; and third, the properties and expression of cell surface transporter proteins. Together these studies provide considerable new insight into the complexity of the signaling mechanisms that regulate the functional activity of the cell.

Ions, channels, and receptors.

Reduction of intracellular Ca(2+) stores (by chelation with the EDTA structural analogue, TPEN) is itself a sufficient trigger of capacitative Ca(2+) entry. TPEN may be a useful tool in studies to investigate the mechanism of capacitative Ca(2+) entry, since potential confounders, such as changes in cytosolic Ca(2+) and second messenger levels, are obviated and the use of pharmacological modifiers of SERCA pumps and Ca(2+) release channels is avoided.

In situ chelation of Ca(2+) in intracellular stores induces capacitative Ca(2+) entry in bovine adrenal chromaffin cells.

The characteristics and properties of the increase in cytosolic [Ca2+] that occurs in bovine adrenal medullary chromaffin cells on exposure to angiotensin 11 have been investigated. In fura-2 loaded cells exposure to a maximally effective concentration of angiotensin II (100 nM) caused a rapid, but transient increase in cytosolic [Ca2+] followed by a lower plateau that was sustained as long as external Ca2+ was present. In the absence of external Ca2+ only the initial brief transient was observed. In cells previously treated with thapsigargin in Ca2+-free medium to deplete the internal Ca2+ stores, angiotensin II caused no increase in cytosolic [Ca2+] when external Ca2+ was absent. Reintroduction of external Ca2+ to thapsigargin-treated, store-depleted cells caused a sustained increase in cytosolic [Ca2+] that was not further increased upon exposure to angiotensin II. Analysis of the data suggests that in bovine chromaffin cells angiotensin II causes Ca2+ entry via a pathway(s) activated as a consequence of internal store mobilization, and entry through this pathway(s) forms the majority of the sustained Ca2+ influx evoked by angiotensin II.

Angiotensin II causes calcium entry into bovine adrenal chromaffin cells via pathway(s) activated by depletion of intracellular calcium stores.

Selecting medical students.

It is increasingly acknowledged that, in addition to prior academic achievement, there is a need to seek evidence for the abilities and personal qualities of applicants to health professional programs at a university. The aim of this study was to determine the specific abilities and personal qualities required for excellence in practice in the relevant professional domains of medical radiation science (MRS).

Assessment of personal qualities in selection of medical radiation science students.

Intellectual aptitude tests and A levels for selecting UK school leaver entrants for medical school.

Selecting medical students: evidence based admissions procedures for medical students are being tested.

AMPA receptors play a critical role in synaptic plasticity and brain development. Here we show that Ca(2+) uptake in response to AMPA receptor activation decreases dramatically during maturation in chicken brain microslices without a change in tissue AMPA receptor content. We found that during maturation the relative concentration of GluR2 subunits increased, the concentration of the AMPA receptor-associated scaffold proteins SAP97 and GRIP decreased and that depolarization increased GluR1 phosphorylation at Ser831 in subcellular fractions enriched in postsynaptic densities at 2 weeks but not at 10 weeks. These changes are all consistent with a decreased Ca(2+) entry through AMPA receptor channels in response to receptor activation and may account for the changes in the functional properties of the receptor, which are thought to underlie, at least in part, the physiological changes that occur with maturation.

David A. Powis

School of Medicine and Public Health

The University of Newcastle

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke