© 1999 American Heart Association, Inc.
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Angiotensin II Type 1 Receptor–Mediated Inhibition of K+ Channel Subunit Kv2.2 in Brain Stem and Hypothalamic Neurons
From the Department of Physiology (C.H.G., J.D.W., M.Z., J.M.M., C.S.), University of Florida College of Medicine, Gainesville, Fla; Department of Physiology and Cell Biology (H.S.M., J.L.K., B.H.), University of Nevada School of Medicine, Reno, Nev.
Correspondence to Dr Craig H. Gelband, University of Florida School of Medicine, Department of Physiology, PO Box 100274, Gainesville, FL 32610. E-mail gelband{at}phys.med.ufl.edu
Abstract—Angiotensin
II (Ang II) has powerful modulatory actions on
cardiovascular function that are mediated by specific
receptors located on neurons within the hypothalamus and brain stem.
Incubation of neuronal cocultures of rat hypothalamus and brain stem
with Ang II elicits an Ang II type 1 (AT1)
receptor–mediated inhibition of total outward K+ current
that contributes to an increase in neuronal firing rate. However, the
exact K+ conductance(s) that is inhibited by Ang II are not
established. Pharmacological manipulation of total neuronal outward
K+ current revealed a component of K+ current
sensitive to quinine, tetraethylammonium,
and 4-aminopyridine, with IC50 values of
21.7 µmol/L, 1.49 mmol/L, and 890 µmol/L,
respectively, and insensitive to 
-dendrotoxin (100 to 500 nmol/L),
charybdotoxin (100 to 500 nmol/L), and mast cell degranulating peptide
(1 µmol/L). Collectively, these data suggest the presence of
Kv2.2 and Kv3.1b. Biophysical examination of the quinine-sensitive
neuronal K+ current demonstrated a macroscopic conductance
with similar biophysical properties to those of Kv2.2 and Kv3.1b. Ang
II (100 nmol/L), in the presence of the AT2 receptor
blocker PD123,319, elicited an inhibition of neuronal K+
current that was abolished by quinine (50 µmol/L). Reverse
transcriptase–polymerase chain reaction analysis confirmed the
presence of Kv2.2 and Kv3.1b mRNA in these neurons. However, Western
blot analyses demonstrated that only Kv2.2 protein was
present. Coexpression of Kv2.2 and the AT1 receptor in
Xenopus oocytes demonstrated an Ang II–induced
inhibition of Kv2.2 current. Therefore, these data suggest that
inhibition of Kv2.2 contributes to the AT1
receptor–mediated reduction of neuronal K+ current and
subsequently to the modulation of cardiovascular function.
Key Words: angiotensin II • Kv2.2 • Kv3.1b AT1 receptor • Xenopus oocyte • cultured neuron
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