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J Neurophysiol 84: 139-151, 2000;
0022-3077/00 $5.00
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The Journal of Neurophysiology Vol. 84 No. 1 July 2000, pp. 139-151
Copyright ©2000 by the American Physiological Society

Major Potassium Conductance in Type I Hair Cells From Rat Semicircular Canals: Characterization and Modulation by Nitric Oxide

James W. Y. Chen1,2 and Ruth Anne Eatock2

 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 MOmega at -67 mV versus 1.3 GOmega 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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