Muraki K, Sasaoka A, Watanabe M, Imaizumi Y
Department of Molecular and Cellular Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
Br J Pharmacol. 2001 Mar;132(5):1154-60. doi: 10.1038/sj.bjp.0703903.
The effects of KRN2391, an ATP-sensitive K+ channel opener (KCO) which also acts as a nitrate, on ionic membrane currents in rabbit femoral arterial myocytes were examined. Under whole-cell clamp conditions where cells were superfused with physiological salts solution containing 5.9 mM K+, KRN2391 elicited an outward current at a holding potential of -30 mV. KRN2391-induced current had a reversal potential of -78 mV and was abolished by glibenclamide (glib). KRN2391 was approximately 25 times more potent than nicorandil to activate an ATP-sensitive K+ current (I:(KATP)). On the other hand, 10 microM KRN2391 did not affect either voltage-dependent Ca(2+) or delayed rectifier K+ channel currents. In the inside-out patch configuration, KRN2391 activated 47 pS K+ channels in the presence of nucleotide diphosphates (NDPs) under the symmetrical 140 mM K+ conditions. Glib and intracellular ATP reversibly inhibited the activity of the 47 pS K+ channels. The 47 pS K+ channels activated by KRN2391 are similar in their conductance and other properties to NDP-sensitive K+ channels (K(NDP) channels) described in other smooth muscles and the cloned channels. KRN2391 is a potent activator of the 47 pS K+ channels and the activation can contribute to the KRN2391-induced vasodilation in arterial muscles.
研究了KRN2391（一种ATP敏感性钾通道开放剂（KCO），同时也作为一种硝酸盐）对兔股动脉肌细胞离子膜电流的影响。在全细胞钳制条件下，用含有5.9 mM钾离子的生理盐溶液灌流细胞，KRN2391在-30 mV的钳制电位下引发外向电流。KRN2391诱导的电流反转电位为-78 mV，并且被格列本脲（glib）阻断。KRN2391激活ATP敏感性钾电流（I:(KATP)）的效力比尼可地尔强约25倍。另一方面，10 microM的KRN2391对电压依赖性钙（2+）通道电流或延迟整流钾通道电流均无影响。在膜内面向外的膜片钳配置中，在对称的140 mM钾离子条件下，KRN2391在存在核苷酸二磷酸（NDPs）的情况下激活了47 pS的钾通道。Glib和细胞内ATP可逆性抑制47 pS钾通道的活性。由KRN2391激活的47 pS钾通道在其电导和其他特性方面与其他平滑肌中描述的NDP敏感性钾通道（K(NDP)通道）以及克隆通道相似。KRN2391是47 pS钾通道的有效激活剂，这种激活可能有助于KRN2391诱导的动脉肌血管舒张。
