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 (tau (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 alpha -dendrotoxin (I-DTX) appeared at -60 mV. Complete block of I-DTX was achieved using either 20 nM alpha -DTX or 50 nM margatoxin. This current activated 10 times faster than I-TEA (tau (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 (IBDS-I) activated around -60 mV. It displayed fast activation (tau (ac), 2.3 +/- 0.4 ms at 250 mV) and fast and complete voltage-dependent inactivation. IBDS-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 IBDS-I varied considerably between neurons. The ratio of the density of IBDS-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.