Hyperpolarization-activated (I(h)) conductances affect brainstem auditory neuron excitability

Blockade of the hyperpolarization-activated cyclic-nucleotide-gated mixed-cationic conductance (I(h)) by ZD7288 markedly reduces excitability of neurons in the superior olivary complex (SOC), in vivo. Following pressure ejection application of 100 microM ZD7288, extracellular recorded single unit responses of 47/47 SOC neurons to monaural or binaural pure tone best frequency (BF) stimuli (30 dB above threshold) decreased by 49.7+/-19%, and background activity decreased by 56.3+/-18.1%. Pressure ejection of the vehicle did not affect excitability. The dose- and time-dependence of ZD7288 (10-100 microM) effects are consistent with specific blockade of I(h) currents. SOC neuron responses to pressure-ejected glutamate were also decreased following application of 100 microM ZD7288 by 76.7+/-28.0%, which suggests a predominant direct effect of ZD7288 on auditory cell excitability. The considerable variability in the magnitude of ZD7288 effects between cells was only partially accounted for by greater effects on neurons with BFs greater than 16 kHz. Therefore, I(h) channels significantly contribute to auditory brainstem neuron excitability, affecting their response level to acoustic stimuli. The variability in the ZD7288 reduction in excitability and its variation with the BF of units could be an indication of regulation and plasticity in neuronal encoding of sounds.