Bisoprolol, Known to Be a Selective β1-Receptor Antagonist, Differentially but Directly Suppresses IK(M) and IK(erg) in Pituitary Cells and Hippocampal Neurons

Abstract

Bisoprolol (BIS) is a selective antagonist of β1 adrenergic receptors. We examined the effects of BIS on M-type K+ currents (IK(M)) or erg-mediated K+ currents (IK(erg)) in pituitary GH3, R1220 cells, and hippocampal mHippoE-14 cells. As GH3 cells were exposed to BIS, amplitude of IK(M) was suppressed with an IC50 value of 1.21 μM. The BIS-induced suppression of IK(M) 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+ (KM) channels, along with decreased mean opening time of the channel. BIS decreased IK(erg) amplitude with an IC50 value of 6.42 μM. Further addition of PD-118057 attenuated BIS-mediated inhibition of IK(erg). 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 IK(M); subsequent application of ML-213(Kv7.2 channel activator) reversed BIS-induced suppression of the current. In hippocampal mHippoE-14 neurons, BIS inhibited IK(M) to a greater extent compared to its depressant effect on IK(erg). This demonstrated that in pituitary cells and hippocampal neurons the presence of BIS is capable of directly and differentially suppressing IK(M) and IK(erg), despite its antagonism of β1-adrenergic receptors.