Cu. Eccles et al., TITYUSTOXIN-K-ALPHA, FROM SCORPION-VENOM, BLOCKS VOLTAGE-GATED, NONINACTIVATING POTASSIUM CURRENT IN CULTURED CENTRAL NEURONS, Neuropharmacology, 33(12), 1994, pp. 1523-1528
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.