title: 4-Aminopyridine effects on summating potentials in the guinea pig.
abstract: DC receptor potentials measured in hair cells, and the associated extracellular DC potential known as the summating potential (SP), originate with nonlinear elements in the mechanoelectric transduction chain. Nonlinear electric conductance has been demonstrated in the basolateral membrane of the hair cell, and is commonly attributed to the presence of voltage- and time-dependent K+ conductances in this part of the hair cell membrane. To study a possible contribution of these K+ channels to the SP we perfused the perilymphatic spaces of the guinea pig cochlea with the K+ channel blocker 4-aminopyridine (4-AP). Since 4-AP might also affect the afferent fibers and, thus, interfere with SP measurement, we added tetrodotoxin (TTX) to the perfusion solutions to block the neuronal discharges. Sound-evoked (2-12 kHz) intracochlear potentials were recorded from the basal turn of both scala vestibuli and scala tympani. The results showed a frequency- and level-dependent effect of 4-AP on the magnitude of the SP. At low and moderate levels of 8 and 12 kHz stimuli 4-AP mostly reduced the SP amplitude, while at high levels of these stimuli and at all levels of 2 and 4 kHz stimuli 4-AP enlarged the SP amplitude. These effects were reversible and occurred in both scala vestibuli and scala tympani. We attribute these bi-directional effects on the SP amplitude to a differential effect of 4-AP on inner hair cell (IHC) and outer hair cell (OHC) physiology. The decrease in SP was found for stimulus conditions where the SP presumably depends mainly on contributions from basal turn IHCs. Blocking the 4-AP-sensitive K+ channel in the IHC membrane should lead to a reduced contribution from the IHCs to the SP, because of an increase in basolateral membrane resistance. The increase in SP was found for stimulus conditions where the SP is assumed to depend mainly on contributions from basal turn OHCs. In this case the OHCs seemed to respond to blocking of the 4-AP-sensitive K+ channel in the basolateral membrane with an increased contribution to the nonlinearity of the transduction chain. Administration of 4-AP did not affect the endocochlear potential. Light microscopic examination revealed no apparent changes in morphology after 4-AP perfusion.
authors.affiliation: Department of Otorhinolaryngology, Utrecht University, The Netherlands. m.g.van_emst@expaud.azu.nl
authors.forename: M G
authors.initials: MG
authors.lastname: van Emst
authors.forename: S F
authors.initials: SF
authors.lastname: Klis
authors.forename: G F
authors.initials: GF
authors.lastname: Smoorenburg
mesh_terms: D015761:4-Aminopyridine / Q000633:toxicity*; D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D001489:Basilar Membrane / Q000187:drug effects / Q000502:physiology; D003055:Cochlear Microphonic Potentials / Q000187:drug effects* / Q000502:physiology; D004553:Electric Conductivity; D005260:Female; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D026902:Potassium Channel Blockers; D015398:Signal Transduction / Q000187:drug effects; D013779:Tetrodotoxin / Q000633:toxicity; D014432:Tympanic Membrane / Q000187:drug effects / Q000473:pathology; D014722:Vestibule, Labyrinth / Q000187:drug effects / Q000473:pathology
chemical_list: D026902:Potassium Channel Blockers; D013779:Tetrodotoxin; D015761:4-Aminopyridine