Bisoprolol (BIS) is a selective antagonist of β 1 adrenergic receptors. We examined the effects of BIS on M-type K + currents (I K(M) ) orerg-mediated K + currents (I K(erg) ) in pituitary GH 3, R1220 cells, and hippocampal mHippoE-14 cells. As GH 3 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 GH 3 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 β 1 -adrenergic receptors.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry