Ca2+ is an important mediator of stimulus-secretion coupling in beta cells of the pancreatic islets, which secrete insulin in response to elevation in plasma glucose concentration. I studied the actions of two lipids, arachidonic acid (AA) and cholesterol, on enzymatically-dissociated single beta cells of rat and mouse, using cytosolic Ca2+ ([Ca2+]i) measurement in conjunction with whole-cell patch-clamp techniques. AA, which is produced in the beta cell upon stimulation with either glucose or acetylcholine, was found to induce a large increase in [Ca2+]i that was dependent on both extracellular Ca2+ entry and intracellular Ca2+ release. Part of the AA-mediated extracellular Ca2+ entry was due to Ca2+ influx through the arachidonate-regulated Ca2+ (ARC) channels, which have not previously been reported in beta cells. The AA-mediated intracellular Ca2+ release was a result of Ca2+ mobilization from multiple inositol trisphosphate (IP3)-sensitive intracellular stores, including the endoplasmic reticulum (ER) and an acidic Ca2+ store that is probably the secretory granules. Therefore, in beta cells, the AA-mediated Ca2+ signal may amplify the [Ca2+]i rise induced by insulin secretagogues. Cholesterol is an integral component of cellular membranes and an important regulator of cellular functions. However, elevation of cholesterol level in the pancreatic islets reduces glucose-stimulated insulin secretion. I found that cholesterol overload impairs the glucose-stimulated [Ca2+]i increase in beta cells by two major mechanisms: the first is a decrease in glucose-stimulated ATP production, which is partly mediated by a decrease in glucose uptake, and the second is the reduction of voltage-gated Ca2+ current density. These effects of cholesterol may partly account for the decreased insulin secretion that develops in patients with type II diabetes, who typically exhibit hypercholesterolemia. In summary, different lipids may mediate beneficial or detrimental effects on Ca2+ regulation in rodent pancreatic beta cells.

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Le mouvement masticatoire est généré et coordonné par un générateur de patron central (GPC) situé au niveau du pont. Plusieurs résultats antérieurs de notre laboratoire soutiennent que le réseau de neurones à l’origine de la rythmogénèse est situé dans le noyau sensoriel principal du nerf trijumeau (NVsnpr). Ces mêmes expériences révèlent que des diminutions de la concentration calcique extracellulaire ([Ca2+]e) tiennent une place importante dans la génération des bouffées de décharges des neurones de cette région. Notre laboratoire tente de vérifier si la contribution des astrocytes à l’homéostasie de la concentration calcique extracellulaire est impliquée dans la genèse du rythme. Cette étude a pour but la caractérisation spatiale du syncytium astrocytaire au sein du NVsnpr dorsal et l’étude de l’effet de la [Ca2+]e sur les propriétés astrocytaires électrophysiologiques et de connectivité. Nous avons utilisés pour ce faire la technique d’enregistrement par patch-clamp sur une préparation en tranche de tronc cérébral de rat. Nous démontrons ici que la diminution de la [Ca2+]e n’affecte pas les propriétés électrophysiologiques astrocytaires, mais induit une augmentation de la taille du syncytium. De plus, nous établissons l’existence au sein du NVsnpr dorsal d’une organisation anatomofonctionnelle du réseau astrocytaire calquée sur l’organisation neuronale. / The masticatory movement is generated and coordinated by a central pattern generator (CPG) located in the pons. Previous results from our laboratory suggest that the neural network responsible for its rythmogenesis is located in the trigeminal main sensory nucleus (NVsnpr). Moreover, results indicate that in this region, decrease in extracellular calcium concentration ([Ca2+]e) plays an important role in genarating burst. One of our laboratory's goal is to assess if the contribution of astrocytes to the extracellular calcium concentration homeostasis is involved in the genesis of the mastication rhythm. With this study, we characterized the astrocyte syncytium within the NVsnpr and measured the effect of [Ca2+]e on the astrocytes electrophysiology and their networks. A patch-clamp recording technique in conjunction with a rat brain stem slice preparation was used. We demonstrate that a decrease in [Ca2+]e does not affect the electrophysiological properties of astrocytes but induces an increase in the size of the syncytium. We also report the existence, within the dorsal NVsnpr, of an anatomofunctional organization between neurons and astrocytes.

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