Maturation of neuronal synapses is thought to involve mitochondria. Bcl-xL protein inhibits mitochondria-mediated apoptosis but may have other functions in healthy adult neurons in which Bcl-xL is abundant. Here, we report that overexpression of Bcl-xL postsynaptically increases frequency and amplitude of spontaneous miniature synaptic currents in rat hippocampal neurons in culture. Bcl-xL, overexpressed either pre or postsynaptically, increases synapse number, the number and size of synaptic vesicle clusters, and mitochondrial localization to vesicle clusters and synapses, likely accounting for the changes in miniature synaptic currents. Conversely, knockdown of Bcl-xL or inhibiting it with ABT-737 decreases these morphological parameters. The mitochondrial fission protein, dynamin-related protein 1 (Drp1), is a GTPase known to localize to synapses and affect synaptic function and structure. The effects of Bcl-xL appear mediated through Drp1 because overexpression of Drp1 increases synaptic markers, and overexpression of the dominant-negative dnDrp1-K38A decreases them. Furthermore, Bcl-xL coimmunoprecipitates with Drp1 in tissue lysates, and in a recombinant system, Bcl-xL protein stimulates GTPase activity of Drp1. These findings suggest that Bcl-xL positively regulates Drp1 to alter mitochondrial function in a manner that stimulates synapse formation.Bcl-2 ͉ synaptic transmission ͉ mitochondria ͉ cell death ͉ ABT-737

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R. Pethig is with the

We have developed a noninvasive instrument called the bioelectric field imager (BFI) for mapping the electric field between the epidermis and the stratum corneum near wounds in both mouse and human skin. Rather than touching the skin, the BFI vibrates a small metal probe with a displacement of 180 μm in air above the skin to detect the surface potential of the epidermis through capacitative coupling. Here we describe our first application of the BFI measuring the electric field between the stratum corneum and epidermis at the margin of skin wounds in mice. We measured an electric field of 177 ± 14 (61) mV/mm immediately upon wounding and the field lines pointed away from the wound in all directions around it. Because the wound current flows immediately upon wounding, this is the first signal indicating skin damage. This electric field is generated at the outer surface of the epidermis by the outward flow of the current of injury. An equal and opposite current must flow within the multilayered epidermis to generate an intraepidermal field with the negative pole at the wound site. Because the current flowing within the multilayered epidermis is spread over a larger area, the current density and subsequent E field generated in that region is expected to be smaller than that measured by the BFI beneath the stratum corneum. The field beneath the stratum corneum typically remained in the 150-200 mV/ mm range for 3 days and then began to decline over the next few days, falling to zero once wound healing was complete. The mean wound field strength decreased by 64 ± 7% following the application of the sodium channel blocker, amiloride, to the skin near the wound and increased by 82 ± 21% following the application of the Cl -channel activator, prostaglandin E2.Electrical signals play an integral role in the function of many of our organ systems and are routinely used in the diagnosis of disease in the heart and nervous system. Our largest organ, the skin, generates a voltage across itself everywhere on the body, yet the signaling function of this "skin battery" remains largely unexplored.This skin battery will drive an ionic current out through any wound where the resistance is low and as this "wound current" flows out of the wound it will in turn generate an electric field within the skin along the lines of current flow. Dubois-Reymond first discovered that ionic currents exit skin wounds 165 years ago using a galvanometer. 1 This was confirmed by Illingworth and Barker 2 using the more modern vibrating probe technique. 3,4 They measured up to 10 μA/cm 2 exiting accidentally amputated fingertips in children during a 2-week period following the injury. This wound current flows through the tissue which has a certain resistivity so this flow must generate an electric field in the skin bordering the has not yet been measured in humans, it has been measured in the skin of guinea pigs, newts, and salamanders (reviewed in 5 ). The lack of human studies is due, in part, to the difficulty of carrying out recordings in hum...