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bioRxiv · 10.1101/328658

A voltage-dependent depolarization induced by low external glucose in neurons of the nucleus of the tractus solitarius of rats: interaction with KATP channels regulated by external glucose.

Murat, C. d. B.·Leao, R.
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Abstract

The brain demands constant supply of glucose-derived energy for cell metabolism and survival, and brain hypoglycemia may compromise synaptic functions. The brainstem nucleus of the tractus solitarius (NTS) is an integrative center for autonomic counterregulatory responses to hypoglycemia, and recent evidences have demonstrated that NTS neurons can also sense fluctuations in glucose levels in the extracellular milieu. Glucose-sensing neurons rely on glucose metabolism to respond to changes in glucose availability, but the ionic mechanisms underlying the low-glucose sensitivity are not well elucidated in NTS neurons. Therefore, this work aimed to investigate the effect of low extracellular glucose (0.5 mM) on the electrophysiological properties of NTS neurons of rats, by whole-cell patch-clamp. We showed that in NTS neurons maintained in 5 mM extracellular glucose, low glucose induces a depolarization in most neurons, which was correlated with membrane potential, decreased with depolarization. ATP-sensitive potassium (KATP) channels contribute to the hyperpolarized resting membrane potential (RMP) of NTS neurons, and blockage of KATP channels produced depolarization of the membrane and occludes the effect of low glucose, thus acting as modulators of low-glucose sensing in NTS neurons. However, this effect is caused by depolarization, since membrane hyperpolarization after KATP blockage restores the effect of low glucose. Additionally, we demonstrated that the incubation of NTS neurons in high glucose (10 mM) prior to recordings leads to more depolarized RMP in these neurons, what contributes to increase the number of neurons unresponsive to a low-glucose challenge, possibly via depolarization by inhibition of KATP channels following increased amounts of high glucose-derived intracellular ATP. We conclude that NTS neurons depolarize the membrane in response to the application of a low-glucose solution, but this effect is occluded by membrane depolarization triggered by KATP blockage. This suggests a homeostatic regulation of the membrane potential by glucose.

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Murat, C. d. B., Leao, R.. 2018-05-22. A voltage-dependent depolarization induced by low external glucose in neurons of the nucleus of the tractus solitarius of rats: interaction with KATP channels regulated by external glucose.. https://doi.org/10.1101/328658

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