碘化N-正丁基氟哌啶醇对豚鼠心房肌细胞乙酰胆碱敏感性钾通道的影响

Effect of N-n-butyl haloperidol iodide on muscarinic K^+ channel in guinea-pig atrial myocytes

目的研究碘化N正丁基氟哌啶醇(F2)对豚鼠心房肌细胞乙酰胆碱敏感性钾通道(KACh)的影响,探讨其对KACh的作用机制。方法采用膜片钳全细胞记录方法,测定F2对原代培养的豚鼠心房肌细胞乙酰胆碱敏感性钾电流IK(ACh)的影响。结果细胞外给予F2对豚鼠心房肌细胞IK(ACh)呈可逆性、浓度依赖性的阻断作用。细胞内添入抗水解的GTP类似物GTPγS后,结果同前。细胞内给予50μmol·L-1F2对IK(ACh)无作用。结论F2是豚鼠心房肌细胞KACh的一种快速通道阻断剂,发挥作用部位在细胞膜外侧,作用位点在钾通道本身,与乙酰胆碱受体无关。

Aim To study the effect of N-n-butyl haloperidol iodide(F_2) on muscarinic K + channel (K_ ACh) in adult guinea-pig atrial myocytes, and try to probe the mechanism of action.Methods The effect of F_2 on muscarinic K + current (I_ K(ACh)) was measured using the whole-cell patch clamp technique in primarily cultured atrial myocytes.Results Extracellular F_2 caused a concentration-dependent inhibition of I_ K(ACh) with an IC_ 50 of 29.15 μmol·L -1. Irreversibly activated I_ K(ACh) in GTP-γ-S loaded cells showed comparable sensitivity to F_2. Intracellular F_2 failed to inhibit I_ K(ACh).Conclusion F_2 blocked K_ ACh in guinea-pig artrial myocytes in an M_2 receptor-independent way from the outside of the cell membrane.