Published Online
on July 5, 2005

A more recent version of this article appeared on August 1, 2005

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Submitted on February 17, 2005
Revised on March 9, 2005

Electrophysiological Properties of Rostral Ventrolateral Medulla Neurons in Angiotensin II 1a Receptor Knockout Mice

Tomokazu Matsuura; Hiroo Kumagai^*; Hiroshi Onimaru; Akira Kawai; Kamon Iigaya; Toshiko Onami; Katsufumi Sakata; Naoki Oshima; Takeshi Sugaya; and Takao Saruta

From the Department of Internal Medicine (T.M., H.K., K.I., T.O., K.S., N.O., T. Saruta), Keio University School of Medicine, Tokyo, Japan; Department of Physiology (H.O., A.K.), Showa University School of Medicine, Tokyo, Japan; and Discovery Laboratory (T. Sugaya), Tanabe Seiyaku Co, Ltd, Osaka, Japan.

^* To whom correspondence should be addressed. E-mail: hkumagai{at}sc.itc.keio.ac.jp.

Abstract--We compared the electrophysiological properties of neurons in the rostral ventrolateral medulla of neonatal angiotensin II type 1a receptor knockout mice and wild-type mice with responses to angiotensin II, its type-1 receptor blocker candesartan, and its type-2 receptor blocker PD123319. Using the whole-cell patch-clamp technique, we examined the characteristics of rostral ventrolateral medulla neurons in brain stem-spinal cord preparations in which the sympathetic neuronal network is preserved. Baseline membrane potential and firing rate were almost similar between angiotensin II type 1a receptor knockout mice and wild-type mice. Superfusion with angiotensin II depolarized rostral ventrolateral medulla bulbospinal neurons in wild-type mice, whereas it hyperpolarized those in angiotensin II type 1a receptor knockout mice. Because pretreatment with candesartan significantly prevented the angiotensin II-induced depolarization in wild-type mice, the angiotensin II type 1 receptor is crucial for this depolarization. Superfusion with PD123319 depolarized rostral ventrolateral medulla bulbospinal neurons in angiotensin II type 1a receptor knockout mice. PD123319 prevented the angiotensin II-induced hyperpolarization in angiotensin II type 1a receptor knockout mice, and, rather, it induced depolarization. These results suggest that the angiotensin II type 2 receptor in rostral ventrolateral medulla plays an antagonistic role against the angiotensin II type 1a receptor in controlling the neuronal activity of rostral ventrolateral medulla.

Key words: angiotensin antagonist • angiotensin II • brain • central nervous system • mice • receptors, angiotensin II • sympathetic nervous system

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