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Messaggio inserito da cidol

I gas nobili Elio, Xenon, Argon, Kripton e altri si possono trovare anche nell'ipotalamo. Cosa si sa in proposito?

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The "inert" gas xenon has been shown to be an effective neuroprotectant in a variety of in vitro and in vivo models of neuronal injury. We examine its neuroprotective properties in an in vitro model of traumatic brain injury. Organotypic hippocampal brain slices from mice pups are subject to a focal mechanical trauma and injury is monitored in the presence and absence of "inert gases" under both normothermic and hypothermic conditions. Neuronal injury is quantified using propidium iodide which becomes fluorescent only when it enters injured cells.

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Abstract

BACKGROUND: Adenosine triphosphate-sensitive potassium (KATP) channels in brain are involved in neuroprotective mechanisms. Pharmacologic activation of these channels is seen as beneficial, but clinical exploitation by using classic K channel openers is hampered by their inability to cross the blood-brain barrier. This is different with the inhalational anesthetic xenon, which recently has been suggested to activate KATP channels; it partitions freely into the brain. METHODS: To evaluate the type and mechanism of interaction of xenon with neuronal-type KATP channels, these channels, consisting of Kir6.2 pore-forming subunits and sulfonylurea receptor-1 regulatory subunits, were expressed in HEK293 cells and whole cell, and excised patch-clamp recordings were performed. RESULTS: Xenon, in contrast to classic KATP channel openers, acted directly on the Kir6.2 subunit of the channel. It had no effect on the closely related, adenosine triphosphate (ATP)-regulated Kir1.1 channel and failed to activate an ATP-insensitive mutant version of Kir6.2. Furthermore, concentration-inhibition curves for ATP obtained from inside-out patches in the absence or presence of 80% xenon revealed that xenon reduced the sensitivity of the KATP channel to ATP. This was reflected in an approximately fourfold shift of the concentration causing half-maximal inhibition (IC50) from 26 4 to 96 6 microm. CONCLUSIONS: Xenon represents a novel KATP channel opener that increases KATP currents independently of the sulfonylurea receptor-1 subunit by reducing ATP inhibition of the channel. Through this action and by its ability to readily partition across the blood-brain barrier, xenon has considerable potential in clinical settings of neuronal injury, including stroke.

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