Computer-simulation studies on roles of potassium currents in neurotransmission of the auditory nerve

Our previous work showed that action potentials (APs) fired in spiral ganglion (SG) neurons broaden gradually as a result of cumulative inactivation of the potassium current (I(K)), or with the application of a tinnitus-inducing drug (quinine). These results led us to speculate that AP width could affect neurotransmission of the auditory nerve under both normal and pathological conditions. This study used both experimental and theoretical approaches to test this hypothesis. We first measured the effect of AP broadening on Ca2+ entry into SG neurons. The effect of pre-synaptic AP broadening on post-synaptic responses was then assessed using computer-simulations. Results showed that wider presynaptic APs augmented responses of all types of postsynaptic glutamatergic receptors mainly by amplifying responses of postsynaptic receptors whose locations were not well aligned with the presynaptic release sites. A cumulative inactivation of I(K) in SG neurons significantly enhanced the responses of kainate receptors at all spike rates, while the augmentations for the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl-D-aspartic acid receptors were most prominent below 100 spikes/s. These modeling results suggest that, in addition to the AP firing rate and timing, the width of APs could affect the neurotransmission of the auditory nerve under both normal and pathological conditions.