Phosphatidylinositol 4,5-bisphosphate is acting as a signal molecule in α1-adrenergic pathway via the modulation of acetylcholine-activated K+ channels in mouse atrial myocytes
Phosphatidylinositol 4,5-bisphosphate is acting as a signal molecule in α1-adrenergic pathway via the modulation of acetylcholine-activated K+ channels in mouse atrial myocytes
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DOI：
10.1074/jbc.m004826200
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发表时间：
2001-01-05
影响因子：
4.8
通讯作者：
Ho, WK
中科院分区：
文献类型：
--
作者：
Cho, H;Nam, GB;Ho, WK
我们研究了α(1)-肾上腺素能激动剂苯肾上腺素（PE）对乙酰胆碱激活的K+电流（I-KACh）的影响。应用膜片钳技术记录小鼠心房肌细胞的I-KACh。10 μ m ACh激活I-KACh后，4 min内电流下降44.27 +/- 2.38% （n = 12）。当PE与ACh一起作用时，脱敏程度明显增加至69.34 +/- 2.22% (n = 9)，表明存在PE诱导的脱敏，I-KACh在6 min水洗后完全恢复脱敏。PE诱导的I- kach脱敏不受蛋白激酶C抑制剂calphostin C的影响，而被磷脂酶C （PLC）抑制剂新霉素抑制。当phophatidylinositol 4,5-bisphosphate （PIP2）的补充被wortmannin （phophatidylinositol 3-kinase和phophatidylinositol 4-kinase的抑制剂）阻断时，I- kach在PE存在下的脱敏进一步增加（97.25 +/- 7.63%,n = 6），并且PE诱导的脱敏恢复受到抑制。冲洗后第二次暴露时I，的振幅降至前一次水平的19.65 +/- 2.61% （n = 6）。这些数据表明，K-ACh通道是由PE通过PLC刺激和PIP2耗竭来调制的。
We have investigated the effect of alpha (1)-adrenergic agonist phenylephrine (PE) on acetylcholine-activated K+ currents (I-KACh). I-KACh was recorded in mouse atrial myocytes using the patch clamp technique. I-KACh was activated by 10 muM ACh and the current decreased by 44.27 +/- 2.38% (n = 12) during 4 min due to ACh-induced desensitization. When PE was applied with ACh, the extent of desensitization was markedly increased to 69.34 +/- 2.22% (n = 9), indicating the presence of PE-induced desensitization, I-KACh was fully recovered from desensitization after a 6-min washout. PE-induced desensitization of I-KACh was not affected by protein kinase C inhibitor, calphostin C, but abolished by phospholipase C (PLC) inhibitor, neomycin, When phophatidylinositol 4,5-bisphosphate (PIP2) replenishment was blocked by wortmannin (an inhibitor of phophatidylinositol 3-kinase and phophatidylinositol 4-kinase), desensitization of I,,, in the presence of PE was further increased (97.25 +/- 7.63%, n = 6), Furthermore, the recovery from PE-induced desensitization was inhibited, and the amplitude of I,, at the second exposure after washout was reduced to 19.65 +/- 2.61% (n = 6) of the preceding level. These data suggest that the K-ACh, channel is modulated by PE through PLC stimulation and depletion of PIP2.