Rostral ventrolateral medulla neuron activity is suppressed by Klotho and stimulated by FGF23 in newborn Wistar rats

• Published in: Autonomic neuroscience 2020-03, Vol.224, p.102640-102640, Article 102640
• Main Authors: Oshima, Naoki, Onimaru, Hiroshi, Yamagata, Akira, Ito, Seigo, Imakiire, Toshihiko, Kumagai, Hiroo
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Animals; Animals, Newborn; FGF23; FGFR1; Fibroblast Growth Factors - pharmacology; Glucuronidase - pharmacology; Hypertension - physiopathology; Klotho; Medulla Oblongata - drug effects; Membrane Potentials - drug effects; Na+/K+-ATPase; Neurons - drug effects; Neurons - physiology; Rats, Wistar; RVLM neurons; Spinal Cord - drug effects; Spinal Cord - physiopathology; Sympathetic Nervous System - physiopathology
• ISSN: 1566-0702; 1872-7484
• DOI: 10.1016/j.autneu.2020.102640

Hypertension often occurs in patients with chronic kidney disease (CKD). Considering the decrease in serum Klotho and increase in serum FGF23 levels in such patients, decreased Klotho and increased FGF23 levels were thought to be associated with hypertension. Presympathetic neurons at the rostral ventrolateral medulla (RVLM) contribute to sympathetic activity and regulation of blood pressure. Therefore, we hypothesized that Klotho would reduce the activities of RVLM neurons and FGF23 would stimulate them. Accordingly, this study examined the effects of Klotho and FGF23 on bulbospinal neurons in the RVLM. We used a brainstem-spinal cord preparation to record from RVLM presympathetic neurons and to evaluate the effects of Klotho and FGF23 on firing rate and membrane potentials of these neurons. Our results showed that Klotho-induced RVLM neuron hyperpolarization, while ouabain, a Na+/K+-ATPase inhibitor, suppressed the effects of Klotho on such neurons. Moreover, FGF23 induced RVLM neuron depolarization, while SU5402, an FGF23 receptor (FGFR1) antagonist, induced RVLM neuron hyperpolarization. Histological examinations revealed that Klotho, Na+/K+-ATPase, FGF23, and FGFR1 were present in RVLM neurons and that Klotho was localized in the same neurons as FGFR1. These results suggest that Klotho and FG23 regulate the activity of RVLM neurons. Klotho may reduce the activity of RVLM neurons via stimulating Na+/K+-ATPase on those neurons while FGF23 may activate those neurons via FGFR1. •Klotho was present in bulbospinal RVLM neurons.•Klotho suppressed the activities of the RVLM neurons via Na+/K+-ATPase.•FGF23 was present in the RVLM neurons.•FGF23 increased the activities of RVLM neurons via FGFR1.•Reduction in Klotho and increase in FGF23 may contribute to a better understanding of hypertension among patients with CKD.