FUNCTION OF ERG (ETHER-A-GO-GO) CHANNELS IN CENTRAL AUDITORY NEURONS
The cochlear nucleus relay auditory information to the higher auditory centers. There are three different cell types, stellate, octopus and bushy, in the ventral cochlear nucleus (VCN). These cells have different electrophysiological and morphological properties. ERG (ether-a-go-go-related gene) channels, belonging to the voltage-gated potassium channel family, have three subgroups with different biophysical properties, ERG1 (Kv11.1), ERG2 (Kv11.2) and ERG3 (Kv11.3). The aim of the current study was to investigate contribution of ERG channels to the passive and active membrane properties of the VCN stellate neurons.
The electrophysiological whole cell-patch clamp technique was used to study the ERG channels in stellate neurons in coronal slices with a thickness of 175-200 μm. The data presented in the current study are based on the recordings from 128 stellate neurons.
Application of terfenadine (10 µM) and E-4031 (10 µM), which are ERG channel antagonists, resulted in increases of input resistance of stellate cells significantly (n = 13; p <0.05). Inactivation of ERG channels by ERG channel antagonists, terfenadine (10 µM) and E-4031 (10 µM), exert excitatory effects upon cell excitability, as indicated by decreased action potential threshold and increased firing rate (n = 10; p<0.01). (p<0.05). Under voltage clamp condition, the E-4031-sensitive tail current first appeared at around -65 mV and the amplitude of the tail current increased gradually with more depolarized membrane potentials. The activation curve for ERG channels was constructed by plotting amplitude of the normalized tail currents as a function of voltage steps. The curve was fitted with a Boltzmann function, which gave a V0.5 -51.2 mV with a slope factor of 6.50.
In conclusion, our results show that stellate neurons express ERG channels, which have similar properties as ERG currents described in other cellular preparations. We think that ERG channels might contribute to setting the threshold, frequency, possibly resting membrane potential, of stellate neurons of the VCN under physiological conditions.
Keywords: ERG channels, patch clamp, electrophysiology, cochlear nucleus, auditory pathway