© 1999 American Heart Association, Inc.
Molecular Medicine |
Oxygen Sensitivity of Cloned Voltage-Gated K+ Channels Expressed in the Pulmonary Vasculature
From the Departments of Physiology (J.T.H., E.A.C., J.R.M, M.M.T.) and Biochemistry and Molecular Biology (M.M.T.), Colorado State University, Ft. Collins, Colo, and the Departament de Bioquimica i Biologia Molecular (A.F.), Universitat de Barcelona, Barcelona, Spain. Joanne T. Hulme is currently affiliated with the Department of Pharmacology, University of Washington, Seattle.
Correspondence to Michael M. Tamkun, Department of Physiology, Colorado State University, Ft. Collins, CO 80523. E-mail tamkunmm{at}lamar.colostate.edu
Abstract—Hypoxic
pulmonary vasoconstriction is initiated by inhibiting one or
more voltage-gated potassium (Kv) channel in the vascular smooth muscle
cells (VSMCs) of the small pulmonary resistance vessels.
Although progress has been made in identifying which Kv channel
proteins are expressed in pulmonary arterial (PA)
VSMCs, there are conflicting reports regarding which channels
contribute to the native O2-sensitive K+
current. In this study, we examined the effects of hypoxia on
the Kv1.2, Kv1.5, Kv2.1, and Kv9.3 
subunits expressed in mouse L
cells using the whole-cell patch-clamp technique. Hypoxia
(PO2=
30 mm Hg) reversibly inhibited
Kv1.2 and Kv2.1 currents only at potentials more positive than 30 mV.
In contrast, hypoxia did not alter Kv1.5 current. Currents
generated by coexpression of Kv2.1 with Kv9.3 subunits were
reversibly inhibited by hypoxia in the voltage range of the
resting membrane potential (EM) of PA VSMCs (28% at
-40 mV). Coexpression of Kv1.2 and Kv1.5 subunits produced
currents that displayed kinetic and pharmacological properties distinct
from Kv1.2 and Kv1.5 channels expressed alone. Moreover,
hypoxia reversibly inhibited Kv1.2/Kv1.5 current
activated at physiologically relevant
membrane potentials (65% at -40 mV). These results indicate that
(1) hypoxia reversibly inhibits Kv1.2 and Kv2.1 but not Kv1.5
homomeric channels, (2) Kv1.2 and 1.5 subunits can assemble to form
an O2-sensitive heteromeric channel, and (3) only
Kv1.2/Kv1.5 and Kv2.1/Kv9.3 heteromeric channels are inhibited by
hypoxia in the voltage range of the PA VSMC EM.
Thus, these heteromeric channels are strong candidates for the
K+ channel isoforms initiating hypoxic pulmonary
vasoconstriction.
Key Words: Kv channel • hypoxia • pulmonary artery • heteromeric
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