High-Threshold K+ Current Increases Gain by Offsetting a Frequency-Dependent Increase in Low-Threshold K+ Current

摘要

High-frequency firing neurons are found in numerous central systems, including the auditory brainstem, thalamus, hippocampus, and neocortex. The kinetics of high-threshold K⁺ currents (IKHT) from the Kv3 subfamily has led to the proposal that these channels offset cumulative Na⁺ current inactivation and stabilize tonic high-frequency firing. However, all high-frequency firing neurons, examined to date, also express low-threshold K⁺ currents (IKLT) that have slower kinetics and play an important role in setting the subthreshold and filtering properties of the neuron. IKLT has also been shown to dampen excitability and is therefore likely to oppose high-frequency firing. In this study, we examined the role of IKHT in pyramidal cells of the electrosensory lobe of weakly electric fish, which are characterized by high-frequency firing, a very wide frequency range, and high levels of IKHT. In particular, we examined the mechanisms that allow IKHT to set the gain of the F-I relationship by interacting with another low-threshold K⁺ current. We found that IKHT increases the gain of the F-I relationship and influences spike waveform almost exclusively in the high-frequency firing range. The frequency dependence arises from IKHT influencing both the IKLT and Na⁺ currents. IKHT thus plays a significant role in stabilizing high-frequency firing by preventing a steady-state accumulation of IKLT that is as important as preventing Na⁺ current inactivation.