Tityustoxin-K alpha, from scorpion venom, blocks voltage-gated, non-inactivating potassium current in cultured central neurons.
Whole-cell voltage-clamp was used to examine the effects of tityustoxin-K alpha (TsTX-K alpha), from the venom of the scorpion Tityus serrulatis, on voltage-gated K+ currents in cultured hippocampal neurons and cerebellar granule cells. Slowly activating, noninactivating outward currents (IK) were generated by depolarizing steps from a holding potential of -60 mV to potentials positive to -40 mV. TsTX-K alpha produced a dose-dependent block of the sustained outward current. The fraction 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 hyperpolarizing prepulse to -100 mV was used to generate a rapidly inactivating current with properties like those of IA. When IA was isolated pharmacologically (with 5-10 mM TEA to block IK) or by subtracting IK from total outward current, TsTX-K alpha had no effect on the IA 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. The data indicate that TsTX-K alpha in cultured mammalian neurons is a potent and selective blocker of a voltage-gated, non-inactivating K+ current with properties like those of a delayed rectifier.
Eccles
C U
CU
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore 21201, USA.
Rogowski
R S
RS
Gu
X
X
Alger
B E
BE
Blaustein
M P
MP
D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000494:pharmacology*
D009498:Neurotoxins; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; C003609:tityustoxin