The number of ganglion cells in the retina of the postnatal rat has been examined. We estimated both the number of axons in the optic nerve and the number of cells which can be retrogradely labelled with horseradish peroxidase from injections into the brain. In the retina of the newborn rat there are at least twice as many ganglion cells as in the adult rat. By retrograde labelling of the ganglion cells and following transection of their axons 24-48 hrs later we can find no evidence that ganglion cells withdraw their axon without degeneration of the patent cell body. We have found that the excess ganglion cells are lost over the first ten postnatal days and during this period we observe pyknotic nuclei in the ganglion cell layer. From our estimates of the total number of neurones in the ganglion cell layer and the number of ganglion cells found at different ages we conclude that the migration of amacrine cells into the ganglion cell layer occurs in the first five postnatal days.

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We investigated the densities of the L-type Ca(2+) current, i(Ca,L), and various Ca(2+) handling proteins in rabbit sinoatrial (SA) node. The density of i(Ca,L), recorded with the whole-cell patch-clamp technique, varied widely in sinoatrial node cells. The density of i(Ca,L) was significantly (p<0.001) correlated with cell capacitance (measure of cell size) and the density was greater in larger cells (likely to be from the periphery of the SA node) than in smaller cells (likely to be from the center of the SA node). Immunocytochemical labeling of the L-type Ca(2+) channel, Na(+)-Ca(2+) exchanger, sarcoplasmic reticulum Ca(2+) release channel (RYR2), and sarcoplasmic reticulum Ca(2+) pump (SERCA2) also varied widely in SA node cells. In all cases there was significantly (p<0.05) denser labeling of cells from the periphery of the SA node than of cells from the center. In contrast, immunocytochemical labeling of the Na(+)-K(+) pump was similar in peripheral and central cells. We conclude that Ca(2+) handling proteins are sparse and poorly organized in the center of the SA node (normally the leading pacemaker site), whereas they are more abundant in the periphery (at the border of the SA node with the surrounding atrial muscle).

␤-Amyloid protein is thought to underlie the neurodegeneration associated with Alzheimer's disease by inducing Ca 2؉ -dependent apoptosis. Elevated neuronal expression of the proinflammatory cytokine interleukin-1␤ is an additional feature of neurodegeneration, and in this study we demonstrate that interleukin-1␤ modulates the effects of ␤-amyloid on Ca 2؉ homeostasis in the rat cortex. ␤-Amyloid-(1-40) (1 M) caused a significant increase in 45 Ca 2؉ influx into rat cortical synaptosomes via activation of L-and N-type voltage-dependent Ca 2؉ channels and also increased the amplitude of N-and P-type Ca 2؉ channel currents recorded from cultured cortical neurons. In contrast, interleukin-1␤ (5 ng/ml) reduced the 45 Ca 2؉ influx into cortical synaptosomes and inhibited Ca 2؉ channel activity in cultured cortical neurons. Furthermore, the stimulatory effects of ␤-amyloid protein on Ca 2؉ influx were blocked following exposure to interleukin-1␤, suggesting that interleukin-1␤ may govern neuronal responses to ␤-amyloid by regulating Ca 2؉ homeostasis.␤-Amyloid (A␤-(1-40)) 1 is a peptide fragment derived from proteolytic processing of ␤-amyloid precursor protein (␤APP) (1), which accumulates as an insoluble extracellular deposit around neurons, giving rise to the senile plaques associated with Alzheimer's disease (AD) (2). Increased neuronal expression of the proinflammatory cytokine interleukin-1␤ (IL-1␤) is an additional neuropathological hallmark of AD (3), and inflammatory mediators such as IL-1␤ have been proposed to contribute to the development of amyloid plaques (4). Several reports describe an interaction between IL-1␤ and A␤ at the processing level; IL-1-immunoreactive microglia are prominent components of amyloid plaques in AD (4), and ␤-amyloid promotes release of IL-1␤ by the glial cells that surround senile plaques (5). In turn, IL-1␤ increases ␤APP mRNA expression (6) and promotes processing of ␤APP to liberate A␤ peptide fragments (7). Thus a chain of events involving IL-1␤ and A␤ is involved in plaque formation; however, the nature of the interaction between IL-1␤ and A␤ at a physiological level is poorly understood. Neuronal apoptosis is the suspected causative factor of neurodegeneration in AD, and A␤ fragments have been shown to promote apoptosis in vitro in human-derived neurotypic cells (8) and cultured neurons (9). The mechanism underlying A␤-induced apoptosis is thought to involve disregulation of Ca 2ϩ homeostasis (10). In the C6 glial cell line, expression of the Ca 2ϩ -binding protein calbindin was found to suppress A␤-induced apoptosis (11), providing evidence for the involvement of Ca 2ϩ fluxes in A␤-induced apoptosis. In this study we report that A␤-(1-40) (i) promotes a stimulation of 45 Ca 2ϩ influx into cortical synaptosomes via activation of L-and N-type voltagedependent Ca 2ϩ channels (VDCCs) and (ii) increases the amplitude of N-and P-type VDCC current in cultured cortical neurons. Furthermore, the A␤-(1-40)-induced increase in Ca 2ϩ influx is blocked by the proinflammatory mediato...

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