Department of Anesthesia, An Nan Hospital, China Medical University, Tainan 70965, Taiwan.
Department of Anesthesia, China Medical University, Taichung 40402, Taiwan.
Int J Mol Sci. 2019 Feb 2;20(3):657. doi: 10.3390/ijms20030657.
Bisoprolol (BIS) is a selective antagonist of β₁ adrenergic receptors. We examined the effects of BIS on M-type K⁺ currents (I) or -mediated K⁺ currents (I) in pituitary GH R1220 cells, and hippocampal mHippoE-14 cells. As GH₃ cells were exposed to BIS, amplitude of I was suppressed with an IC value of 1.21 μM. The BIS-induced suppression of I amplitude was not affected by addition of isoproterenol or ractopamine, but attenuated by flupirtine or ivabradine. In cell-attached current, BIS decreased the open probability of M-type K⁺ (K) channels, along with decreased mean opening time of the channel. BIS decreased I amplitude with an IC value of 6.42 μM. Further addition of PD-118057 attenuated BIS-mediated inhibition of I. Under current-clamp conditions, BIS depolarization increased the firing of spontaneous action potentials in GH₃ cells; addition of flupirtine, but not ractopamine, reversed BIS-induced firing rate. In R1220 cells, BIS suppressed I; subsequent application of ML-213(Kv7.2 channel activator) reversed BIS-induced suppression of the current. In hippocampal mHippoE-14 neurons, BIS inhibited I to a greater extent compared to its depressant effect on I. This demonstrated that in pituitary cells and hippocampal neurons the presence of BIS is capable of directly and differentially suppressing I and I, despite its antagonism of β₁-adrenergic receptors.
比索洛尔（BIS）是一种β₁肾上腺素能受体的选择性拮抗剂。我们研究了 BIS 对垂体 GH R1220 细胞和海马 mHippoE-14 细胞中 M 型 K⁺电流（I）或β介导的 K⁺电流（I）的影响。当 GH₃ 细胞暴露于 BIS 时，I 幅度被抑制，IC 值为 1.21 μM。BIS 诱导的 I 幅度抑制不受异丙肾上腺素或ractopamine 的影响，但被 flupirtine 或 ivabradine 减弱。在细胞贴附电流中，BIS 降低了 M 型 K⁺（K）通道的开放概率，同时通道的平均开放时间缩短。BIS 以 6.42 μM 的 IC 值降低 I 幅度。进一步加入 PD-118057 可减弱 BIS 介导的 I 抑制。在电流钳条件下，BIS 去极化增加 GH₃ 细胞中自发性动作电位的发放；加入 flupirtine，但不是 ractopamine，可逆转 BIS 诱导的发放率。在 R1220 细胞中，BIS 抑制 I；随后应用 ML-213（Kv7.2 通道激活剂）逆转 BIS 诱导的电流抑制。在海马 mHippoE-14 神经元中，BIS 对 I 的抑制作用比对 I 的抑制作用更大。这表明，在垂体细胞和海马神经元中，尽管 BIS 拮抗β₁肾上腺素能受体，但它能够直接且有差异地抑制 I 和 I。
