Sánchez-Alonso J L, Halliwell J V, Colino A
Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain.
Neurosci Lett. 2008 Jul 18;439(3):275-80. doi: 10.1016/j.neulet.2008.05.016. Epub 2008 May 10.
Many studies have used the channel blocker ZD 7288 to assess possible physiological and pathophysiological roles of hyperpolarization-activated cation currents (Ih). In view of the known interplay between Ih and other membrane conductances, the effects in Wistar rats of ZD 7288 on low-voltage-activated (LVA (- or T-type)) Ca2+ channels were examined in whole-cell patch-clamp recordings from CA1 pyramidal cells in the presence of TTX, TEA, 4-AP, CsCl, BaCl2 and nifedipine. ZD 7288 reduced T-type calcium channel currents and this effect was concentration dependant. ZD 7288 blocked T-type currents when applied extracellularly, but not when included in the recording pipette. Furthermore, ZD 7288 altered the steady-state voltage-dependent inactivation of T-currents. These results indicate that the blocker ZD 7288 has effects on voltage sensitive channels additional to those reported for the Ih current.
许多研究已使用通道阻滞剂ZD 7288来评估超极化激活阳离子电流(Ih)可能的生理和病理生理作用。鉴于Ih与其他膜电导之间已知的相互作用,在存在TTX、TEA、4-AP、CsCl、BaCl2和硝苯地平的情况下,通过全细胞膜片钳记录,研究了ZD 7288对Wistar大鼠CA1锥体细胞中低电压激活(LVA(-或T型))Ca2+通道的影响。ZD 7288降低了T型钙通道电流,且这种作用呈浓度依赖性。当细胞外应用ZD 7288时可阻断T型电流,但记录电极内加入时则无此作用。此外,ZD 7288改变了T电流的稳态电压依赖性失活。这些结果表明,阻滞剂ZD 7288除了对Ih电流有报道的作用外,对电压敏感通道也有影响。