Three Types of Depolarization-Activated Potassium Currents in Acutely Isolated Mouse Vestibular Neurons

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Abstract
The nature and electrophysiological properties of Ca2+-independent depolarization-activated potassium currents were investigated in vestibular primary neurons acutely isolated from postnatal mice using the whole cell configuration of the patch-clamp technique. Three types of currents were identified. The first current, sensitive to TEA ( ITEA) and insensitive to 4-aminopyridine (4-AP), activated at −40 mV and exhibited slow activation ( τac, 38.4 ± 7.8 ms at −30 mV, mean ± SD). ITEAhad a half activation potential [ Vac(1/2)] of −14.5 ± 2.6 mV and was inactivated by up to 84.5 ± 5.7% by 10-s conditioning prepulses with a half inactivation potential [ Vinac(1/2)] of −62.4 ± 0.2 mV. The second current, sensitive to 4-AP (maximum block around 0.5 mM) and to α-dendrotoxin ( IDTX) appeared at −60 mV. Complete block of IDTXwas achieved using either 20 nM α-DTX or 50 nM margatoxin. This current activated 10 times faster than ITEA( τac, 3.5 ± 0.8 ms at −50 mV) with Vac(1/2)of −51.2 ± 0.6 mV, and inactivated only slightly compared with ITEA(maximum inactivation, 19.7 ± 3.2%). The third current, also sensitive to 4-AP (maximum block at 2 mM), was selectively blocked by application of blood depressing substance (BDS-I; maximum block at 250 nM). The BDS-I–sensitive current ( IBDS-I) activated around −60 mV. It displayed fast activation ( τac, 2.3 ± 0.4 ms at −50 mV) and fast and complete voltage-dependent inactivation. IBDS-Ihad a Vac(1/2)of −31.3 ± 0.4 mV and Vinac(1/2)of −65.8 ± 0.3 mV. It displayed faster time-dependent inactivation and recovery from inactivation than ITEA. The three types of current were found in all the neurons investigated. Although ITEAwas the major current, the proportion of IDTXand IBDS-Ivaried considerably between neurons. The ratio of the density of IBDS-Ito that of IDTXranged from 0.02 to 2.90 without correlation with the cell capacitances. In conclusion, vestibular primary neurons differ by the proportion rather than the type of the depolarization-activated potassium currents they express.