title: Major potassium conductance in type I hair cells from rat semicircular canals: characterization and modulation by nitric oxide.
abstract: 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, I(K, L), which activates at relatively negative voltages. We used whole cell and patch configurations to study I(K,L) in hair cells isolated from the sensory epithelia of rat semicircular canals. I(K,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 I(K,L) was activated at the resting potential, the cells had low input resistances (R(m)): 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 (V(R) = -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 Ca(2+) channels (positive to -60 mV) that mediate transmitter release? One possibility, suggested by spontaneous positive shifts in the activation range of I(K,L) during whole cell recording, is that the activation range might be modulated in vivo. Any factor that reduces the number of I(K,L) channels open at V(R) will increase R(m) and depolarize V(R). Nitric oxide (NO) is an ion channel modulator that is present in vestibular epithelia. Four different NO donors, applied externally, inhibited the I(K,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 I(K,L). Ca(2+)-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 Ca(2+) influx, to NO production and inhibition of I(K,L). The resulting increase in R(m) would augment the receptor potential, a form of positive feedback.
authors.affiliation: Neuroscience Program, University of Rochester, Rochester, New York 14642, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Chen
authors.forename: R A
authors.initials: RA
authors.lastname: Eatock
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D005942:Gluconates / Q000493:pharmacokinetics; D006162:Guanylate Cyclase / Q000378:metabolism; D018069:Hair Cells, Vestibular / Q000201:enzymology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D051381:Rats; D020318:Rats, Long-Evans; D012665:Semicircular Canals / Q000166:cytology* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D005942:Gluconates; D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; C110881:S-nitro-N-acetylpenicillamine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; C002385:linsidomine; D015761:4-Aminopyridine; D008981:Molsidomine; D006162:Guanylate Cyclase; D010396:Penicillamine; D006152:Cyclic GMP; C030691:gluconic acid; D011188:Potassium