4-AMINOPYRIDINE EFFECTS ON SUMMATING POTENTIALS IN THE GUINEA-PIG

DC receptor potentials measured in hair cells, and the associated extr acellular DC potential known as the summating potential (SP), originat e with nonlinear elements in the mechanoelectric transduction chain. N onlinear 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 ha ir cell membrane. To study a possible contribution of these K+ channel s to the SP we perfused the perilymphatic spaces of the guinea pig coc hlea with the K+ channel blocker 4-aminopyridine (4-AP). Since 4-AP mi ght also affect the afferent fibers and, thus, interfere with SP measu rement, we added tetrodotoxin (TTX) to the perfusion solutions to bloc k the neuronal discharges. Sound-evoked (2-12 kHz) intracochlear poten tials were recorded from the basal turn of both scala vestibuli and sc ala tympani. The results showed a frequency- and level-dependent effec t 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-dire ctional effects on the SP amplitude to a differential effect of 4-AP o n inner hair cell (IHC) and outer hair cell (OHC) physiology. The decr ease in SP was found for stimulus conditions where the SP presumably d epends mainly on contributions from basal turn IHCs. Blocking the 4-AP -sensitive Ki channel in the IHC membrane should lead to a reduced con tribution from the IHCs to the SP, because of an increase in basolater al membrane resistance. The increase in SP was found for stimulus cond itions where the SP is assumed to depend mainly on contributions from basal turn OHCs. In this case the OHCs seemed to respond to blocking o f the 4-AP-sensitive K+ channel in the basolateral membrane with an in creased contribution to the nonlinearity of the transduction chain. Ad ministration of 4-AP did not affect the endocochlear potential. Light microscopic examination revealed no apparent changes in morphology aft er 4-AP perfusion.