ACUTE EFFECT OF ALDOSTERONE ON THE MEMBRANE POTENTIAL IN NEURONS OF THE NUCLEUS OF THE SOLITARY TRACT

Abstract

IntroductionA population of neurons in the nucleus of the solitary tract (NTS) expresses both the mineralocorticoid receptor (MR) and the enzyme 11β‐hydroxysteroid dehydrogenase type 2 (HSD2), making these neurons responsive to aldosterone, not to glucocorticoids. HSD2 neurons in the NTS contribute to the development of sodium appetite which is stimulated by a combination of body sodium deficiency and low blood volume, a condition that activates the renin‐angiotensin‐aldosterone system. The effect of aldosterone in the NTS to induce sodium appetite may involve non‐genomic mechanisms, independent of nuclear MR, gene transcription and protein synthesis.ObjectiveIn the present study, we investigated the acute effect of aldosterone on the membrane potential of NTS neurons in brainstem slices of rats.MethodologyMale Holtzman rats (150 to 250 g) were decapitated and the brainstem rapidly removed and submerged in ice‐cold artificial cerebrospinal fluid (aCSF) with osmolality of 300–310 mosmol/KgH2O and pH 7.4. Brainstem coronal slices were obtained and then placed in the recording chamber, which was continuously perfused with oxygenated aCSF with or without aldosterone at room temperature. Whole‐cell patch‐clamp recordings of NTS neurons were done in current‐clamp mode to measure the membrane potential. Data are shown as mean ± SEM, and statistical significance was determined by unpaired Student's t‐test using the GraphPad Prism software. Experimental protocols were approved by the Ethics Committee for Animal Care and Use (CEUA 13/2018).ResultsAldosterone (1 □M) caused cell depolarization and increased firing frequency of action potentials (0.8 ± 0.2 Hz, *** p < 0.001), in silent NTS neurons. Only 30% of the recorded neurons (6 of 20 neurons) showed a reversible depolarization in response to aldosterone and repolarization upon washout.ConclusionThe present results suggest that aldosterone, acting via non‐genomic mechanisms, can depolarize and increase the firing frequency of action potentials in NTS neurons in vitro. These cells (possibly HSD2 neurons) might be those involved in the development of sodium appetite induced by aldosterone.Support or Funding InformationFunding: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.