Nitric oxide uncouples gap junctions of supporting Deiters cells from Corti's organ.
Supporting cells of Corti's organ are electrically coupled via gap junctions. They probably serve to maintain the unique cochlear environment that is required for normal sensory function. In this study we used input capacitance measurements under whole-cell voltage-clamp conditions to evaluate the effects of nitric oxide on gap junctional communication between pairs of isolated supporting Deiters cells. We show that the nitric oxide (NO) donor sodium nitroprusside causes the uncoupling of Deiters cells, and that an NO synthase inhibitor blocks the effect. The cGMP analogue 8-bromo-cGMP also uncouples Deiters cells. With either treatment, the input capacitance of pairs of Deiters cells drops to single-cell levels within minutes of application, indicative of electrical uncoupling. We surmise that the NO/cGMP pathway may serve to modulate normal cochlear homeostasis and possibly plays a role in ototoxic mechanisms.
Blasits
S
S
Section of Otolaryngology, Yale University School of Medicine, New Haven, CT 06510, USA.
Maune
S
S
Santos-Sacchi
J
J
D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009925:Organ of Corti / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
D020030:Nitric Oxide Donors; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D006152:Cyclic GMP