Klöckner U, Isenberg G
Eur J Pharmacol. 1986 Aug 15;127(3):165-71. doi: 10.1016/0014-2999(86)90360-2.
The calcium currents (ICa) of isolated smooth muscle cells (urinary bladder of the guinea-pig) were analyzed at 35 degrees C and 3.6 mM [Ca]0. The whole cells were voltage-clamped with a single patch electrode which was filled with 150 mM CsCl in order to block potassium outward currents. Tiapamil reduced ICa at concentrations between 1 microM (threshold) and 0.5 mM (complete block). Administration of 10 microM tiapamil at rest reduced ICa by 10% ('initial block'). Repetitive depolarizations (140 ms long pulses to -5 mV, applied at 1 Hz) reduced ICa further in a beat-to-beat fashion. This 'conditioned block' developed with a faster time course and to a greater extent when the stimulation frequency was increased and when the holding potentials were set to more positive levels. Reduction of ICa by tiapamil was facilitated by more positive and attenuated by more negative holding potentials. The influence of holding potential and pulse frequency on the tiapamil effect is discussed in terms of the 'modulated receptor hypothesis'.
在35摄氏度和3.6 mM [Ca]0条件下，对分离的平滑肌细胞（豚鼠膀胱）的钙电流（ICa）进行了分析。用单个膜片电极对全细胞进行电压钳制，电极内充150 mM CsCl以阻断钾外向电流。蒂帕米在1 microM（阈值）至0.5 mM（完全阻断）的浓度范围内可降低ICa。静息时给予10 microM蒂帕米可使ICa降低10%（“初始阻断”）。重复去极化（140 ms长脉冲至 -5 mV，以1 Hz频率施加）可使ICa逐搏进一步降低。当刺激频率增加以及钳制电位设定为更正的水平时，这种“条件性阻断”以更快的时间进程且在更大程度上发生。蒂帕米对ICa的降低作用在更正的钳制电位下更易发生，而在更负的钳制电位下则减弱。根据“调制受体假说”讨论了钳制电位和脉冲频率对蒂帕米效应的影响。
