Functional and pharmacological properties of canine ERG potassium channels
| Autor: | Jerzy Karczewski, Kimberly Della Penna, Jixin Wang, Joseph J. Salata, Thomas M. Connolly, Hao Wang, Kenneth S. Koblan, Paul B. Bennett |
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| Rok vydání: | 2003 |
| Předmět: |
ERG1 Potassium Channel
medicine.medical_specialty Patch-Clamp Techniques Potassium Channels Physiology Blotting Western Binding Competitive Cell Line Dogs Piperidines Physiology (medical) Internal medicine Gene expression Potassium Channel Blockers medicine Animals Humans Benzopyrans Patch clamp Ion channel Staining and Labeling Voltage-gated ion channel Chemistry Electric Conductivity Temperature Biological activity Ether-A-Go-Go Potassium Channels Potassium channel Cell biology Kinetics Endocrinology Potassium Channels Voltage-Gated Cell culture Immunologic Techniques Potassium Cardiology and Cardiovascular Medicine Ion Channel Gating |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 284:H256-H267 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00220.2002 |
| Popis: | We established HEK-293 cell lines that stably express functional canine ether-à-go-go-related gene (cERG) K+ channels and examined their biophysical and pharmacological properties with whole cell patch clamp and35S-labeled MK-499 ([35S]MK-499) binding displacement. Functionally, cERG current had the hallmarks of cardiac delayed rectifier K+ current ( I Kr). Channel opening was time- and voltage dependent with threshold near −40 mV. The half-maximum activation voltage was −7.8 ± 2.4 mV at 23°C, shifting to −31.9 ± 1.2 mV at 36°C. Channels activated with a time constant of 13 ± 1 ms at +20 mV, showed prominent inward rectification at depolarized potentials, were highly K+ selective (Na+-to-K+permeability ratio = 0.007), and were potently inhibited by I Kr blockers. Astemizole, terfenadine, cisapride, and MK-499 inhibited cERG and human ERG (hERG) currents with IC50 values of 1.3, 13, 19, and 15 nM and 1.2, 9, 14, and 21 nM, respectively, and competitively displaced [35S]MK-499 binding from cERG and hERG with IC50 values of 0.4, 12, 35, and 0.6 nM and 0.8, 5, 47, and 0.7 nM, respectively. cERG channels had biophysical properties appropriate for canine action potential repolarization and were pharmacologically sensitive to agents known to prolong QT. A novel MK-499 binding assay provides a new tool to detect agents affecting ERG channels. |
| Databáze: | OpenAIRE |
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