A physiologically based model of discharge pattern regulation by transient K+ currents in cochlear nucleus pyramidal cells.

Pyramidal cells in the dorsal cochlear nucleus (DCN) show three characteristic discharge patterns in response tones: pauser, buildup, and regular firing. Experimental evidence suggests that a rapidly inactivating K+ current (I(KIF)) plays a critical role in generating these discharge patterns. To explore the role of I(KIF), we used a computational model based on the biophysical data. The model replicated the dependence of the discharge pattern on the magnitude and duration of hyperpolarizing prepulses, and I(KIF) was necessary to convey this dependence. Phase-plane and perturbation analyses show that responses to depolarization are critically controlled by the amount of inactivation of I(KIF). Experimentally, half-inactivation voltage and kinetics of I(KIF) show wide variability. Varying these parameters in the model revealed that half-inactivation voltage, and activation and inactivation rates, controls the voltage and time dependence of the model cell discharge. This suggests that pyramidal cells can adjust their sensitivity to different temporal patterns of inhibition and excitation by modulating the kinetics of I(KIF). Overall, I(KIF) is a critical conductance controlling the excitability of DCN pyramidal cells.