Wegener J W, Nawrath H
Pharmakologisches Institut, Universität Mainz, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1995 Sep;352(3):322-30. doi: 10.1007/BF00168564.
The effects of the phenylalkylamines verapamil, gallopamil, and devapamil on L-type calcium currents (ICa) were studied in ventricular myocytes from rat hearts using the whole-cell patch-clamp technique. In particular, the question was addressed, whether the pharmacological binding sites for these drugs were located at the inner and/or at the outer surface of the cell membrane. Therefore, tertiary verapamil, gallopamil, and devapamil and their corresponding quaternary derivatives were applied either from the outside or the inside of the cell membrane. Extracellular application of verapamil, gallopamil and devapamil (each at 3 microM) reduced ICa to 16.1 +/- 8.6%, 11 +/- 8.9%, and 9.3 +/- 6% of control, respectively. Intracellular application of the same substances, via the patch pipette filled with 30 microM of either verapamil, gallopamil, or devapamil, failed to depress ICa. The quaternary derivatives of the phenylalkylamines (30 microM) were ineffective both when applied extracellularly or intracellularly. It is suggested that phenylalkylamines block ICa in ventricular myocytes by acting on a binding site of the calcium channel molecule located at the outer surface of the cell membrane.
运用全细胞膜片钳技术，研究了苯烷基胺类药物维拉帕米、加洛帕米和地伐帕米对大鼠心室肌细胞L型钙电流（ICa）的影响。特别要探讨的问题是，这些药物的药理学结合位点是位于细胞膜的内表面还是外表面。因此，将叔维拉帕米、加洛帕米和地伐帕米及其相应的季铵衍生物分别从细胞膜外侧或内侧施加。细胞外施加维拉帕米、加洛帕米和地伐帕米（各为3微摩尔）时，ICa分别降至对照的16.1±8.6%、11±8.9%和9.3±6%。通过充满30微摩尔维拉帕米、加洛帕米或地伐帕米的膜片吸管向细胞内施加相同物质，未能抑制ICa。苯烷基胺类药物的季铵衍生物（30微摩尔）无论细胞外或细胞内施加均无作用。提示苯烷基胺类药物通过作用于位于细胞膜外表面的钙通道分子结合位点来阻断心室肌细胞的ICa。
