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

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 ( I TEA) and insensitive to 4-aminopyridine (4-AP), activated at −40 mV and exhibited slow activation ( τ ac, 38.4 ± 7.8 ms at −30 mV, mean ± SD). I TEA had a half activation potential [ V ac(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 [ V inac(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 ( I DTX) appeared at −60 mV. Complete block of I DTX was achieved using either 20 nM α-DTX or 50 nM margatoxin. This current activated 10 times faster than I TEA( τ ac, 3.5 ± 0.8 ms at −50 mV) with V ac(1/2) of −51.2 ± 0.6 mV, and inactivated only slightly compared with I TEA (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 ( I BDS-I) activated around −60 mV. It displayed fast activation ( τ ac, 2.3 ± 0.4 ms at −50 mV) and fast and complete voltage-dependent inactivation. I BDS-I had a V ac(1/2) of −31.3 ± 0.4 mV and V inac(1/2) of −65.8 ± 0.3 mV. It displayed faster time-dependent inactivation and recovery from inactivation than I TEA. The three types of current were found in all the neurons investigated. Although I TEA was the major current, the proportion of I DTX and I BDS-I varied considerably between neurons. The ratio of the density of I BDS-I to that of I DTX ranged 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.