A voltage-dependent depolarization induced by low external glucose in neurons of the nucleus of the tractus solitarius: interaction with K-ATP channels

Author(s)

Murat, Cahue De Bernardis ^[1] ; Leao, Ricardo Mauricio ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF PHYSIOLOGY-LONDON; v. 597, n. 9, p. 2515-2532, MAY 1 2019.
• Web of Science Citations: 0

Abstract

Key points Neurons from the brainstem nucleus of the tractus solitarius (NTS) participate in the counter-regulatory mechanisms in response to hypoglycaemia. ATP-sensitive potassium (K-ATP) channels are expressed in NTS neurons, and are partially open at rest in normoglycaemic 5 mM glucose. In normoglycaemic conditions, most NTS neurons depolarize in response to low external glucose (0.5 mM), via a voltage-dependent mechanism. Conversely, most NTS neurons incubated in hyperglycaemic 10 mM glucose do not respond to low glucose due to a more positive resting membrane potential caused by the closure of K-ATP channels following increased intracellular metabolic ATP. Our findings show that in hyperglycaemic conditions, NTS neurons failed to sense rapid changes in external glucose, which could be related to hypoglycaemia-associated autonomic failure. The nucleus of the tractus solitarius (NTS) is an integrative centre for autonomic counter-regulatory responses to hypoglycaemia. K-ATP channels link the metabolic status of the neuron to its excitability. Here we investigated the influence of K-ATP channels on the membrane potential of NTS neurons in normo- and hyperglycaemic external glucose concentrations, and after switching to a hypoglycaemic concentration, using in vitro electrophysiological recordings in brainstem slices. We found that in normoglycaemic (5 mM) glucose, tolbutamide, a K-ATP channel antagonist, depolarized the membrane of most neurons, and this effect was observed in more hyperpolarized neurons. All neurons hyperpolarized after pharmacological activation of K-ATP channels. Most NTS neurons depolarized in the presence of low glucose (0.5 mM), and this effect was only seen in hyperpolarized neurons. The effect of glucose was caused by a cationic current with a reversal potential around -50 mV. In the presence of hyperglycaemic glucose (10 mM), neurons were more depolarized, and fewer neurons responded to K-ATP blockage. Application of 0.5 mM glucose solution to these neurons depolarized the membrane only in more hyperpolarized neurons. We conclude that NTS neurons present with K-ATP channels open at rest in normoglycaemic conditions, and their membrane potential is affected by extracellular glucose. Moreover, 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 K-ATP blockage. Our data suggest a homeostatic regulation of the membrane potential by external glucose, and a possible mechanism related to the hypoglycaemia-associated autonomic failure. (AU)

• FAPESP's process: 16/01607-4 - High intensity sound stimulation and synaptic plasticity
• Grantee: Ricardo Mauricio Xavier Leão
• Support Opportunities: Regular Research Grants