Three types of depolarization-activated potassium currents in acutely isolated mouse vestibular neurons

The nature and electrophysiological properties of Ca(2+)-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 (I(BDS-I)) activated around -60 mV. It displayed fast activation (tau(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.