DiFrancesco D
Università di Milano, Dipartimento di Fisiologia e Biochimica Generali, Elettrofisiologia, Italy.
Pflugers Arch. 1994 May;427(1-2):64-70. doi: 10.1007/BF00585943.
Block of the hyperpolarization-activated "pacemaker" current (i(f)) by the bradycardic agent UL-FS 49 was studied in isolated sino-atrial (SA) node myocytes. Using repetitive activation/deactivation protocols, micromolar concentrations of UL-FS 49 blocked i(f) in a dose-dependent fashion. Block development was slow, with time constants decreasing with drug concentration and ranging from 25.8 s at 10 microM to 75.5 s at 1 microM UL-FS 49. Block did not develop in cells held at -35 mV, at which voltage i(f) channels are closed, indicating that channels must open before blocking occurs. Apparently in contrast with the requirement of negative voltages for block development, block was relieved by hyperpolarization with a time course slower than current kinetics. Due to the hyperpolarization-induced block relief, current/voltage (I/V) relations in the presence of UL-FS 49 displayed inward-going rectification. Experimental data fitted the hypothesis that UL-FS 49 behaves as an "open channel" blocker of "single-ion" i(f) channels. Block occurs within the pore, at a distance of about 39% of the membrane thickness from its internal side.
在分离的窦房（SA）结心肌细胞中研究了致心动过缓药物UL-FS 49对超极化激活的“起搏”电流（i(f)）的阻断作用。使用重复激活/失活方案，微摩尔浓度的UL-FS 49以剂量依赖方式阻断i(f)。阻断的发展缓慢，时间常数随药物浓度降低，在10 microM的UL-FS 49时为25.8秒，在1 microM时为75.5秒。在保持在-35 mV的细胞中未出现阻断，在该电压下i(f)通道关闭，这表明通道必须在阻断发生前打开。显然与阻断发展需要负电压的情况相反，超极化可缓解阻断，其时间进程比电流动力学慢。由于超极化诱导的阻断缓解，在存在UL-FS 49的情况下电流/电压（I/V）关系呈现内向整流。实验数据符合UL-FS 49作为“单离子”i(f)通道的“开放通道”阻断剂的假设。阻断发生在孔内，距离膜内侧约为膜厚度的39%。
