Hassinen Minna's research while affiliated with University of Eastern Finland and other places

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Publications (1)

FIGURE 1. Current-voltage relationship of I Ks generated by zebrafish KCNQ1 and KCNQ + KCNE1 channels in CHO cells. CHO cells were transfected either with KCNQ1 only (1:0) or with KCNQ1 and KCNE1 in a 3:1 plasmid ratio. A, Representative recordings of currents generated by KCNQ1 channels (left) and voltage dependence of activation kinetics (time-to-peak current) of I Ks (right). B, Representative recordings of currents generated by KCNQ1 + KCNE1 channels (left) and voltage dependence of activation kinetics (t) of I Ks (right). The arrowheads indicate the times from which the current was measured. C, Mean (6SEM) current-voltage relationship generated by KCNQ1 and KCNQ1 + KCNE1 channels and cell transfected with GFT plasmid only. The voltage protocol used to elicit the delayed rectifier current is shown in the inset of A. The results are means (6SEM) of 22 and 24 cells for KCNQ1 and KCNQ1 + KCNE1, respectively. Asterisks indicate statistically significant differences (P , 0.05) between the channel assemblies.
FIGURE 2. A, Concentration-response curves of currents generated by zebrafish KCNQ1 and KCNQ + KCNE1 channels in CHO cells to chromanol 293B (left) and representative recordings of I Ks currents in the absence and presence of the drug (right). The arrowheads indicate the times from which the current was measured. B, Concentration-response curves of currents generated by zebrafish KCNQ1 and KCNQ + KCNE1 channels in CHO cells to HMR-1556 (left) and representative recordings of I Ks currents in the absence and presence of the drug (right). The voltage protocol used to elicit the I Ks peak current is shown in the inset of A. Concentration for half-maximal inhibition of the current (IC 50 ) is given within the figure. Asterisks indicate statistically significant differences (P , 0.05) between the channel assemblies. The results are means (6SEM) of 12-14 cells.
FIGURE 3. A, Concentration-response curves of currents generated by zebrafish KCNQ1 and KCNQ + KCNE1 channels in CHO cells to R-L3 (left) and representative recordings of I Ks currents (right). The arrowheads indicate the times from which the current was measured. B, Concentration-response curves of currents generated by zebrafish KCNQ1 and KCNQ + KCNE1 channels in CHO cells to mefenamic acid (left) and representative recordings of I Ks currents (right). The voltage protocol used to elicit the I Ks peak current is shown in the inset of A. Concentration for half-maximal inhibition of the current (IC 50 ) is given within the figure. Note that at the concentration of 0.01 mM, the current was slightly higher than in the control. Asterisks indicate statistically significant differences (P , 0.05) between the channel assemblies. The results are means (6SEM) of 12-14 cells.
Concentrations for Half-Maximal Inhibition (IC 50 ) of Mammalian and Zebrafish I Ks Current to Chromanol 293B and HMR-1556
Effect of channel assembly (KCNQ1 or KCNQ1 + KCNE1) on the response of zebrafish IKs current to IKs inhibitors and activators
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January 2022

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57 Reads

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2 Citations

Journal of Cardiovascular Pharmacology

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Hassinen Minna

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In cardiac myocytes, the slow component of the delayed rectifier K+ current (IKs) ensures repolarization of action potential during beta-adrenergic activation or when other repolarizing K+ currents fail. As a key factor of cardiac repolarization IKs should be present in model species used for cardiovascular drug screening, preferably with pharmacological characteristics similar to those of the human IKs. To this end, we investigated the effects of inhibitors and activators of the IKs on KCNQ1 and KCNQ1+KCNE1 channels of the zebrafish, an important model species, in Chinese hamster ovary cells. Inhibitors of IKs, chromanol 293B and HMR-1556, inhibited zebrafish IKs channels with approximately similar potency as that of mammalian IKs. Chromanol 293B concentration for half-maximal inhibition (IC50) of zebrafish IKs was at 13.1+/-5.8 and 13.4+/-2.8 [micro]M for KCNQ1 and KCNQ1+KCNE1 channels, respectively. HMR-1556 was a more potent inhibitor of zebrafish IKs channels with IC50=0.1+/-0.1 [micro]M and 1.5+/-0.8 [micro]M for KCNQ1 and KCNQ1+KCNE1 channels, respectively. R-L3 and mefenamic acid, generally identified as IKs activators, both inhibited zebrafish IKs. R-L3 almost completely inhibited the current generated by KCNQ1 and KCNQ1+KCNE1 channels with similar potency (IC50 1.1+/-0.4 and 1.0+/-0.4 [micro]M, respectively). Mefenamic acid partially blocked zebrafish KCNQ1 (IC50=9.5+/-4.8 [micro]M) and completely blocked KCNQ1+KCNE1 channels (IC50=3.3+/-1.8 [micro]M). Although zebrafish IKs channels respond to IKs inhibitors in the same way as mammalian IKs channels, they response to activators is atypical, probably due to the differences in the binding domain of KCNE1 to KCNQ1. Therefore, care must be taken when translating the results from zebrafish to humans.

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