Bisoprolol, Known to Be a Selective β₁-Receptor Antagonist, Differentially but Directly Suppresses I and I in Pituitary Cells and Hippocampal Neurons.

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.