A herg-like potassium current regulates the resting membrane potential in glomus
cells of the rabbit carotid body.
Ficker, Jeffrey L. Overholt and Eckhard, Tianen Yang, Hashim Shams, Gary R. Bright
and Nanduri R. Prabhakar.
Departments of @Physiology and Biophysics and #Rammelkamp Center for
Education and Research, Case Western Reserve University, School of Medicine,
Cleveland, OH 44106-4970
APStracts 7:0008J, 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) 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 TEA, 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.
Received 15 July 1999; accepted in final form 4 November 1999.
APS Manuscript Number J591-9.
Article publication pending J Neurophysiol
ISSN 1080-4757 Copyright 2000 The American Physiological Society.
Published in APStracts on 18 January 2000