Bisoprolol, Known to Be a Selective β<sub>1</sub>-Receptor Antagonist, Differentially but Directly Suppresses I<sub>K(M)</sub> and I<sub>K(erg)</sub> in Pituitary Cells and Hippocampal Neurons

oleh: Edmund Cheung So, Ning-Ping Foo, Shun Yao Ko, Sheng-Nan Wu

Format: Article
Diterbitkan: MDPI AG 2019-02-01

Deskripsi

Bisoprolol (BIS) is a selective antagonist of &#946;<sub>1</sub> adrenergic receptors. We examined the effects of BIS on M-type K<sup>+</sup> currents (I<sub>K(M)</sub>) or <i>erg</i>-mediated K<sup>+</sup> currents (I<sub>K(erg)</sub>) in pituitary GH<sub>3,</sub> R1220 cells, and hippocampal mHippoE-14 cells. As GH<sub>3</sub> cells were exposed to BIS, amplitude of I<sub>K(M)</sub> was suppressed with an IC<sub>50</sub> value of 1.21 &#956;M. The BIS-induced suppression of I<sub>K(M)</sub> 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<sup>+</sup> (K<sub>M</sub>) channels, along with decreased mean opening time of the channel. BIS decreased I<sub>K(erg)</sub> amplitude with an IC<sub>50</sub> value of 6.42 &#956;M. Further addition of PD-118057 attenuated BIS-mediated inhibition of I<sub>K(erg)</sub>. Under current-clamp conditions, BIS depolarization increased the firing of spontaneous action potentials in GH<sub>3</sub> cells; addition of flupirtine, but not ractopamine, reversed BIS-induced firing rate. In R1220 cells, BIS suppressed I<sub>K(M)</sub>; subsequent application of ML-213(Kv7.2 channel activator) reversed BIS-induced suppression of the current. In hippocampal mHippoE-14 neurons, BIS inhibited I<sub>K(M)</sub> to a greater extent compared to its depressant effect on I<sub>K(erg)</sub>. This demonstrated that in pituitary cells and hippocampal neurons the presence of BIS is capable of directly and differentially suppressing I<sub>K(M)</sub> and I<sub>K(erg)</sub>, despite its antagonism of &#946;<sub>1</sub>-adrenergic receptors.