Effects of midazolam on hERG K+ channel / 中国应用生理学杂志
Chinese Journal of Applied Physiology
;
(6): 143-147, 2015.
Article
in Chinese
| WPRIM
| ID: wpr-243397
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of midazolam on human ether-a-go-go (hERG) K+ channels exogenously expressed in human embryonic kidney cells (HEK-293) and the underlying molecular mechanisms.</p><p><b>METHODS</b>Whole-cell patch clamp technique was used to record WT, Y652A and F656C hERG K+ current expressed in HEK-293 cells.</p><p><b>RESULTS</b>Midazolam inhibited hERG K+ current in a concentration-dependent manner, the half-maximum block concentrations (IC50) values were (1.31 ± 0.32) µmol/L. The half-activation voltage (V1/2) were (2.32 ± 0.38) mV for the control and (-1.96 ± 0.83) mV for 1.0 µmol/L midazolam. The half-inactivation voltage (V1/2) was slightly shifted towards negative voltages from (-49.25 ± 0.69) mV in control to (-57.53 ± 0.53) mV after 1.0 µmol/L midazolam (P < 0.05). Mutations in drug-binding sites (Y652A or F656C) of the hERG channel significantly attenuated the hERG current blockade by midazolam.</p><p><b>CONCLUSION</b>Midazolam can block hERG K+ channel and cause the speed of inactivation faster. Mutations in the drug-binding sites (Y652 or F656) of the hERG channel were found to attenuate hERG current blockage by midazolam.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Midazolam
/
Patch-Clamp Techniques
/
Potassium Channel Blockers
/
Dose-Response Relationship, Drug
/
Ether-A-Go-Go Potassium Channels
/
HEK293 Cells
/
Mutation
Limits:
Humans
Language:
Chinese
Journal:
Chinese Journal of Applied Physiology
Year:
2015
Type:
Article
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