PT  - JOURNAL ARTICLE
AU  - Xin Wang
AU  - Ai Ying Xiao
AU  - Tomomi Ichinose
AU  - Shan Ping Yu
TI  - Effects of Tetraethylammonium Analogs on Apoptosis and Membrane Currents in Cultured Cortical Neurons
DP  - 2000 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 524--530
VI  - 295
IP  - 2
4099  - http://jpet.aspetjournals.org/content/295/2/524.short
4100  - http://jpet.aspetjournals.org/content/295/2/524.full
SO  - J Pharmacol Exp Ther2000 Nov 01; 295
AB  - Tetraethylammonium (TEA), the quaternary ammonium ion and nonselective K+ channel blocker, is protective against neuronal apoptosis. We now tested two TEA analogs, tetrapentylammonium (TPeA) and tetrahexylammonium (THA), for their effects on apoptotic neuronal death and for their pharmacological profiles on membrane currents in cultured mouse cortical neurons. TPeA and THA (0.1–1.0 μM) attenuated staurosporine-induced caspase-3 activation and neuronal apoptosis. TPeA and THA blocked the outward delayed rectifier K+ (IK) current in concentration-dependent manners with IC50 values of 2.7 and 1.9 μM, respectively. IK was blocked by TPeA in a use-dependent manner, whereas THA blockedIK regardless of activation state of the channel. TPeA at 1 μM inhibited the high voltage-activated (HVA) Ca2+ current and the A-type K+ current (IA). TPeA (1–10 μM) also blocked the fast inactivating Na+ current. The ligand-gatedN-methyl-d-aspartate (NMDA) receptor current was not affected by up to 20 μM TPeA. THA at 1 μM showed inhibitory effects on IA, HVA Ca2+, and Na+ currents. THA (10 μM) suppressed NMDA currents. The data suggest that, as K+ channel blockers and apoptosis antagonists, TPeA and THA are much more potent than TEA; however, they have nonspecific actions on several voltage-gated or ligand-gated channels. The American Society for Pharmacology and Experimental Therapeutics