| Abstract No.: | C-E3159 |
| Country: | Canada |
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| Title: | SODIUM DETECTION IS AN INTRINSIC PROPERTY OF THE RAT MNPO NEURONS: IMPORTANCE OF A TTX-INSENSITIVE LEAK SODIUM CHANNEL |
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| Authors/Affiliations: | 1 Christina Tremblay*;
1 Laval University, Centre de recherche du CHUL (CHUQ), Unités de Neurosciences, Québec, QC, Canada
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| Content: | An elevated sodium (Na+) concentration in the body fluid compartments might be correlated with salt-sensitive hypertension. With this respect, the brain Na+ sensors, which are essential in the regulation of Na+ homeostasis might be a cellular determinant of this cardiovascular disease. A large neuronal population of the median preoptic nucleus (MnPO) of the rat has been shown to be sensitive to variation in extracellular Na+ concentration. The cellular mechanism underlying Na+ detection in the MnPO is based on the hypothesis that Na+ sensing is an intrinsic property of the MnPO neurons. The aim of the present study is to determine whether the change in membrane potential elicited by a change in the extracellular Na+ level is specifically carried by Na+ influx through a leak channel, putatively the NaX channel. The permeability of the leak channel to various ions will be also determined. Whole-cell patch clamp recordings were performed on acutely dissociated MnPO neurons obtained from young male Wistar rats (3-4 weeks old). In MnPO neurons held at their resting potential, bath application of three extracellular solutions increased in Na+ concentration triggered an inward current of increased amplitude. By contrast, a pure osmotic stimulus (mannitol solution :350 mOsm) did not generate any current. In order to identify the ion carrying the current elicited by the high Na+-containing solutions, voltage ramps were generated before and at the peak of the Na+-induced current. To record this current in isolation, voltage-activated currents, like TTX-sensitive sodium, potassium and calcium currents were blocked with appropriate pharmacological compounds present in both the intra and extracellular solutions. Our results indicate that the reversal potential of the Na+-induced current was similar to the reversal potential of the Na+ ion calculated from the Nernst equation. The permeability of the leak channel to lithium (94 %), guanidine (20%) and rubidium (0%) was compared to Na+ (100%). The present study indicates that dissociated MnPO neurons are genuine Na+ sensors and not osmoreceptors. Detection of the extracellular Na+ level is achieved by the specific influx of Na+ ions through a leak channel. Our results also demonstrate that the permeability of the leak channel to some ions was similar to the permeability of the Na+ TTX-sensitive channel to these ions. The identity of the leak Na+ channel remains to be clarified. However, the presence of NaX channel mRNA in the MnPO makes the NaX channel a good candidate. |
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