Abstract
Bisoprolol (BIS) is a selective antagonist of β₁ adrenergic receptors. We examined the effects of BIS on M-type K⁺ currents (I(K(M))) or erg-mediated K⁺ currents (I(K(erg))) in pituitary GH(3,) R1220 cells, and hippocampal mHippoE-14 cells. As GH₃ cells were exposed to BIS, amplitude of I(K(M)) was suppressed with an IC(50) value of 1.21 μM. The BIS-induced suppression of I(K(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⁺ (K(M)) channels, along with decreased mean opening time of the channel. BIS decreased I(K(erg)) amplitude with an IC(50) value of 6.42 μM. Further addition of PD-118057 attenuated BIS-mediated inhibition of I(K(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 I(K(M)); subsequent application of ML-213(Kv7.2 channel activator) reversed BIS-induced suppression of the current. In hippocampal mHippoE-14 neurons, BIS inhibited I(K(M)) to a greater extent compared to its depressant effect on I(K(erg)). This demonstrated that in pituitary cells and hippocampal neurons the presence of BIS is capable of directly and differentially suppressing I(K(M)) and I(K(erg)), despite its antagonism of β₁-adrenergic receptors.