I h and HCN Channels in Murine Spiral Ganglion Neurons: Tonotopic Variation,Local Heterogeneity,and Kinetic Model

One of the major contributors to the response profile of neurons in the auditory pathways is the I _h current. Its properties such as magnitude, activation, and kinetics not only vary among different types of neurons (Banks et al., J Neurophysiol 70:1420–1432, 1993; Fu et al., J Neurophysiol 78:2235–2245, 1997; Bal and Oertel, J Neurophysiol 84:806–817, 2000; Cao and Oertel, J Neurophysiol 94:821–832, 2005; Rodrigues and Oertel, J Neurophysiol 95:76–87, 2006; Yi et al., J Neurophysiol 103:2532–2543, 2010), but they also display notable diversity in a single population of spiral ganglion neurons (Mo and Davis, J Neurophysiol 78:3019–3027, 1997), the first neural element in the auditory periphery. In this study, we found from somatic recordings that part of the heterogeneity can be attributed to variation along the tonotopic axis because I _h in the apical neurons have more positive half-activation voltage levels than basal neurons. Even within a single cochlear region, however, I _h current properties are not uniform. To account for this heterogeneity, we provide immunocytochemical evidence for variance in the intracellular density of the hyperpolarization-activated cyclic nucleotide-gated channel α-subunit 1 (HCN1), which mediates I _h current. We also observed different combinations of HCN1 and HCN4 α-subunits from cell to cell. Lastly, based on the physiological data, we performed kinetic analysis for the I _h current and generated a mathematical model to better understand varied I _h on spiral ganglion function. Regardless of whether I _h currents are recorded at the nerve terminals (Yi et al., J Neurophysiol 103:2532-2543, 2010) or at the somata of spiral ganglion neurons, they have comparable mean half-activation voltage and induce similar resting membrane potential changes, and thus our model may also provide insights into the impact of I _h on synaptic physiology.