Olesen S P, Munch E, Moldt P, Drejer J
Department of Cellular Biology, NeuroSearch A/S, Glostrup, Denmark.
Eur J Pharmacol. 1994 Jan 4;251(1):53-9. doi: 10.1016/0014-2999(94)90442-1.
Activators and blockers of specific ion channels are important pharmacological tools for characterizing ion channels and their influence on cell function. The large-conductance Ca(2+)-dependent K+ channel (BK channel) is blocked by peptides such as charybdotoxin and iberiotoxin, but no selective activator of the channel has been described. Here we report single-channel and whole-cell patch-clamp experiments on the specific activation of BK channels in aortic smooth muscle cells with a new heterocyclic molecule, NS 1619 (1-(2'-hydroxy-5'-trifluoromethylphenyl)-5-trifluoromethyl- 2(3H)benzimidazolone). The effect of NS 1619 on the BK channel was dose-dependent, resulting in a shift of the activation curve by up to -50 mV towards negative membrane potentials. The effect was fully reversible and was antagonized by charybdotoxin as well as by tetraethylammonium ions. The compound hyperpolarized the smooth muscle cells. NS 1619 is a selective and new type of K+ channel activator, which may significantly modulate cell excitability.
特定离子通道的激活剂和阻滞剂是表征离子通道及其对细胞功能影响的重要药理学工具。大电导钙依赖性钾通道（BK通道）可被诸如蝎毒素和iberiotoxin等肽阻断，但尚未发现该通道的选择性激活剂。在此，我们报告了用一种新的杂环分子NS 1619（1-（2'-羟基-5'-三氟甲基苯基）-5-三氟甲基-2（3H）苯并咪唑酮）对主动脉平滑肌细胞中BK通道的特异性激活进行的单通道和全细胞膜片钳实验。NS 1619对BK通道的作用呈剂量依赖性，导致激活曲线向负膜电位方向最多偏移-50 mV。该作用完全可逆，并被蝎毒素以及四乙铵离子拮抗。该化合物使平滑肌细胞超极化。NS 1619是一种选择性新型钾通道激活剂，可能显著调节细胞兴奋性。
