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The Journal of Neurophysiology Vol. 83 No. 3 March 2000, pp. 1150-1157
Copyright ©2000 by the American Physiological Society
1Departments of Physiology and Biophysics and 2Rammelkamp Center for Education and Research, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4970
Overholt, Jeffrey L.,
Eckhard Ficker,
Tianen Yang,
Hashim Shams,
Gary R. Bright, and
Nanduri R. Prabhakar.
HERG-Like Potassium Current Regulates the Resting Membrane
Potential in Glomus Cells of the Rabbit Carotid Body. J. Neurophysiol. 83: 1150-1157, 2000. Direct evidence for a
specific K+ channel underlying the resting membrane
potential in glomus cells of the carotid body has been absent. The
product of the human ether-a-go-go-related gene (HERG) produces inward
rectifier currents that are known to contribute to the resting membrane
potential in other neuronal cells. The goal of the present study was to
determine whether carotid body glomus cells express HERG-like
K+ current, and if so, to determine whether a HERG-like
current regulates the resting membrane potential. Freshly dissociated rabbit glomus cells under whole cell voltage clamp exhibited slowly decaying outward currents that activated 20-30 mV positive to the
resting membrane potential. Raising extracellular K+
revealed a slowly deactivating inward tail current indicative of
HERG-like K+ current. HERG-like currents were not found in
cells resembling type II cells. The HERG-like current was blocked by
dofetilide (DOF) in a concentration-dependent manner
(IC50 = 13 ± 4 nM, mean ± SE) and
high concentrations of Ba2+ (1 and 10 mM). The biophysical
and pharmacological characteristics of this inward tail current suggest
that it is conducted by a HERG-like channel. The steady-state
activation properties of the HERG-like current
(Vh = 
44 ± 2 mV) suggest that
it is active at the resting membrane potential in glomus cells. In
whole cell, current-clamped glomus cells (average resting membrane
potential, 48 ± 4 mV), DOF, but not tetraethylammonium, caused
a significant (13 mV) depolarizing shift in the resting membrane
potential. Using fluorescence imaging, DOF increased
[Ca2+]i in isolated glomus cells. In an
in-vitro carotid body preparation, DOF increased basal sensory
discharge in the carotid sinus nerve in a concentration-dependent
manner. These results demonstrate that glomus cells express a HERG-like
current that is active at, and responsible for controlling the resting
membrane potential.
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