TITYUSTOXIN-K-ALPHA, FROM SCORPION-VENOM, BLOCKS VOLTAGE-GATED, NONINACTIVATING POTASSIUM CURRENT IN CULTURED CENTRAL NEURONS

Whole-cell voltage-clamp was used to examine the effects of tityustoxi n-K alpha (TsTX-K alpha), from the venom of the scorpion Tityus serrul atis, on voltage-gated K+ currents in cultured hippocampal neurons and cerebellar granule cells. Slowly activating, noninactivating outward currents (I-K) were generated by depolarizing steps from a holding pot ential of -60 mV to potentials positive to -40 mV. TsTX-K alpha produc ed a dose-dependent block of the sustained outward current. The fracti on of total current blocked ranged from 10 to 60% over a concentration range of 2.5-120 nM in both cerebellar and hippocampal neurons. A hyp erpolarizing prepulse to - 100 mV was used to generate a rapidly inact ivating current with properties like those of I-A. When I-A was isolat ed pharmacologically (with 5-10 mM TEA to block I-K) or by subtracting I-K from total outward current, TsTX-K alpha had no effect on the I-A in either cell type. TsTX-K alpha also had no apparent effect on the leak conductance or on the inward rectifier current in these cells. Th e data indicate that TsTX-K alpha in cultured mammalian neurons is a p otent and selective blocker of a voltage-gated, non-inactivating K+ cu rrent with properties like those of a delayed rectifier.