Electropharmacological analysis of the regulation of the cardiac K^+ channels by inositol trisphosphate.

毒蕈碱乙酰胆碱受体操作的K^+电流（IK.ACh）在窦房结自动性和心房动作电位复极化的调节中起重要作用。我们检测了嘌呤能P2-、内皮素ET-、缓激素B_2-、组胺h_1受体介导的fik调控。膜片钳法测定离体豚鼠心房细胞乙酰胆碱含量。1) Nakaya，合作研究者报道了腺苷-5'-三磷酸腺苷（ATP）引起IK的双相变化。乙酰胆碱，通过p2purinoreceptor激活，短暂升高后持续降低（Hara & Nakaya，欧洲药物杂志，324:295-303,1997）。2) Nakaya也报道了ET-3而不是et - 1对预激活IK的抑制作用。细胞内负荷肌醇1,4,5-三磷酸腺苷（IP_3）几乎可以消除乙酰氨基甲酸酯（ACh），表明IP_3的参与（Yamaguchi et al ., Am J Physiol 273: H1745-H1753, 1997）。3)我们报道过缓激肽明显抑制IK。蛋白激酶C （PKC）抑制剂calphostin C或酪氨酸激酶（TK）抑制剂染料木素可减弱乙酰胆碱通过B_2受体激活和缓激肽的抑制作用，提示B_2受体介导的TK或PKC的激活可能参与了IK的发生。乙酰胆碱对乙酰胆碱的抑制作用[J] .中国生物医学工程学报，2003,19(2):326 - 326。4)组胺（THIS）引起IK双相变化。乙酰胆碱通过Hi受体。虽然HIS对IK有抑制作用。PKC和TK抑制剂对乙酰胆碱（ACh）的抑制作用不明显，细胞内加载磷脂酰肌醇4,5-二磷酸（PIP_2）可显著减弱HIS对乙酰胆碱（IK.ACh）的抑制作用。这些结果表明，PIP2的水解可能参与了h_1受体介导的IK抑制。乙酰胆碱，细胞内信号转导系统参与IK有一些差异。这些受体之间的乙酰胆碱调节。

The muscarinic acetyicholine receptor-operated K^+ current (IK.ACh) plays an important role in the regulation of sinus node automaticity and atrial action potential repolarization. We examined purinergic P2-, endothelin ET-, bradykinin B_2-, histamine H_1-receptor-mediated the regulation ofIK.ACh in isolated guinea-pig atrial cells by use of the patch-clamp technique. 1) Nakaya, co-investigator, has reported that adenosin-5'-triphosphate (ATP) produced biphasic changes of IK.ACh, a transient increase followed by a sustained decrease, through P_2purinoceptor activation (Hara & Nakaya, Eur J Pharmacol, 324 : 295-303, 1997). 2) Nakaya has also reported that the inhibitory effect of ET-3 but not ET-l on the preactivated IK.ACh was almost abolished by intracellular loading of inositol 1,4,5-trisphosphate (IP_3), indicating the involvement of IP_3 (Yamaguchi et al, Am J Physiol 273 : H1745-H1753, 1997). 3) We have reported that bradykinin markedly inhibited IK.ACh through B_2 receptor activation and the inhibitory effect of bradykinin was attenuated by calphostin C, a protein kinase C (PKC) inhibitor, or genistein, a tyrosine kinase (TK) inhibitor, indicating that B_2-receptor-mediated activation ofTK or PKC may be involved in the IK.ACh inhibition (Sakamoto et al, Br J Pharmacol 125 : 283-292, 1998). 4) Histamine (THIS) produced biphasic changes of IK.ACh through Hi receptors. Although the inhibitory effect of HIS on IK.ACh was not affected by PKC or TK inhibitor, intracellular loading of phosphatidylinositol 4,5-bisphosphate (PIP_2) significantly attenuated the inhibitory effect of HIS on IK.ACh. These results suggest that PIP2 hydrolysis may be involved in the H_1-receptor-mediated inhibition of IK.ACh, and that there are some differences in the intracellular signal transduction system involved in the IK.ACh regulation among these receptors.