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The Journal of Neurophysiology Vol. 84 No. 1 July 2000, pp. 139-151
Copyright ©2000 by the American Physiological Society
1Neuroscience Program, University of Rochester, Rochester, New York 14642; and 2The Bobby R. Alford Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, Texas 77030
Chen, James W. Y. and
Ruth Anne Eatock.
Major Potassium Conductance in Type I Hair Cells From Rat
Semicircular Canals: Characterization and Modulation by Nitric Oxide. J. Neurophysiol. 84: 139-151, 2000. Mammalian vestibular organs have two types of hair cell, type I and
type II, which differ morphologically and electrophysiologically. Type
I hair cells alone express an outwardly rectifying current, IK,L, which activates at relatively negative voltages. We
used whole cell and patch configurations to study
IK,L in hair cells isolated from the sensory
epithelia of rat semicircular canals. IK,L
was potassium selective, blocked by 4-aminopyridine, and permeable to
internal cesium. It activated with sigmoidal kinetics and was
half-maximally activated at
74.5 ± 1.6 mV
(n = 35; range
91 to
50 mV). It was a very
large conductance (91 ± 8 nS at
37 mV; 35 nS/pF for a cell of
average size). Patch recordings from type I cells revealed a candidate
ion channel with a conductance of 20-30 pS. Because
IK,L was activated at the resting potential, the cells had low input resistances (Rm):
median 25 M
at
67 mV versus 1.3 G
for type II cells.
Consequently, injected currents comparable to large transduction
currents (300 pA) evoked small (
10 mV) voltage responses. The cells'
small voltage responses and negative resting potentials
(VR =
81.3 ± 0.2 mV,
n = 144) pose a problem for afferent
neurotransmission: how does the receptor potential depolarize the cell
into the activation range of Ca2+ channels (positive to
60 mV) that mediate transmitter release? One possibility, suggested
by spontaneous positive shifts in the activation range of
IK,L during whole cell recording, is that the activation range might be modulated in vivo. Any factor that reduces the number of IK,L channels open at
VR will increase
Rm and depolarize
VR. Nitric oxide (NO) is an ion channel
modulator that is present in vestibular epithelia. Four different NO
donors, applied externally, inhibited the
IK,L conductance at
67 mV, with mean
effects ranging from 33 to 76%. The NO donor sodium nitroprusside
inhibited channel activity in patches when they were cell-attached but
not excised, suggesting an intracellular cascade. Consistent with an
NO-cGMP cascade, 8-bromo-cGMP also inhibited whole cell
IK,L. Ca2+-dependent NO synthase
is reported to be in hair cells and nerve terminals in the vestibular
epithelium. Excitatory input to vestibular organs may lead, through
Ca2+ influx, to NO production and inhibition of
IK,L. The resulting increase in
Rm would augment the receptor potential, a
form of positive feedback.
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