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.

Characterization of the Inhibitory Effect of Gastrodigenin and Gastrodin on M-type K+ Currents in Pituitary Cells and Hippocampal Neurons

“…Once the whole-cell mode was firmly achieved, the examined cells were maintained at −50 mV, and a depolarizing pulse of −10 mV with a duration of 1 s was subsequently applied to evoke a unique population of K + currents, namely I K(M) , as previously identified [15]. As depicted in Figure 1, the presence of HBA caused a progressive decrease in the density of I K(M) in these cells in a timeand concentration-dependent manner.…”

“…Each solution (e.g., the bath and pipette solutions) was filtered on the day of use with a disposable syringe filter with a 0.22 µm pore size (Millipore, Bedford, MA, USA). [15]. The culture medium was changed every 2-3 days for the removal of non-adhering cells, and cells were passaged as they reached confluence.…”

Characterization of Perturbing Actions by Verteporfin, a Benzoporphyrin Photosensitizer, on Membrane Ionic Currents

“…In addition to I K(DR) , another type of K + current [i.e., I K(M) ] detected in GH 3 cells (Sankaranarayanan and Simasko, 1996; Stojilkovic et al, 2010; So et al, 2019) was further designed to evaluate whether the presence of VP has any modifications on this type of K + current. To amplify I K(M) , we bathed cells in high-K + (145 mM), Ca 2+ -free solution, the composition of which is described in Materials and Methods .…”

“…During the measurements, the pipette with a resistance of 3–5 MΩ, which was inserted into holder, was gently maneuvered by using a WR-98 micromanipulator (Narishige). Patch-clamp experiments were measured in either cell-attached, inside-out, or whole-cell arrangement by using an RK-400 patch-clamp amplifier (Bio-Logic, Claix, France) connected with a personal computer with 64-bit processor (Lin et al, 2004; Wu et al, 2017; So et al, 2019). Shortly before giga-seal formation was achieved, the potentials were appropriately corrected for the liquid junction potential that commonly develop at the pipette tip as the composition of the pipette solution was quite different from that in the bath.…”

Characterization of Effectiveness in Concerted Ih Inhibition and IK(Ca) Stimulation by Pterostilbene (Trans-3,5-dimethoxy-4′-hydroxystilbene), a Stilbenoid

“…All solutions were prepared using deionized water from a Milli-Q water purification system (APS Water Services, Inc., Van Nuys, CA, USA), and both the pipette solution and culture medium used were commonly filtered on the day of use with a sterile Acrodisc ® filter with a 0.2-µm Supor ® membrane (Pall Corp., Port Washington, NY, USA). [65][66][67][68]. mHippoE-14 cells were maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum and 2 mL l-glutamine.…”