Abstract
Originalsprog | Engelsk |
---|---|
Tidsskrift | Pflügers Archiv: European Journal of Physiology |
Vol/bind | 446 |
Udgave nummer | 5 |
Sider (fra-til) | 607-16 |
Antal sider | 9 |
ISSN | 0031-6768 |
DOI | |
Status | Udgivet - 2003 |
Bibliografisk note
Keywords: Animals; CHO Cells; Calcium Channel Agonists; Cricetinae; Humans; Indoles; Ion Channel Gating; KCNQ Potassium Channels; Kidney; Membrane Potentials; Patch-Clamp Techniques; Potassium Channels; Potassium Channels, Voltage-GatedAdgang til dokumentet
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Voltage-independent KCNQ4 currents induced by (+/-)BMS-204352. / Schrøder, Rikke Louise; Strøbaek, Dorte; Olesen, Søren-Peter; Christophersen, Palle.
I: Pflügers Archiv: European Journal of Physiology, Bind 446, Nr. 5, 2003, s. 607-16.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Voltage-independent KCNQ4 currents induced by (+/-)BMS-204352.
AU - Schrøder, Rikke Louise
AU - Strøbaek, Dorte
AU - Olesen, Søren-Peter
AU - Christophersen, Palle
N1 - Keywords: Animals; CHO Cells; Calcium Channel Agonists; Cricetinae; Humans; Indoles; Ion Channel Gating; KCNQ Potassium Channels; Kidney; Membrane Potentials; Patch-Clamp Techniques; Potassium Channels; Potassium Channels, Voltage-Gated
PY - 2003
Y1 - 2003
N2 - The compound BMS-204352 has been targeted for use against acute ischemic stroke, due to its activation of the large-conductance Ca2+-activated K-channel (BK). We have previously described that the racemate (+/-)BMS-204352 reversibly modulates KCNQ4 voltage dependency. Here we show that (+/-)BMS-204352 also induces a voltage-independent KCNQ4 current. The channels were stably expressed in human embryonic kidney cells (HEK293), and investigated by use of the whole-cell mode of the patch-clamp technique. (+/-)BMS-204352 was applied extracellularly (10 microM) in order to precipitate the robust appearance of the voltage-independent current. The voltage-independent KCNQ4 currents were recorded as instantaneous increases in currents upon hyperpolarizing or depolarizing voltage steps elicited from holding potentials of -90 or -110 mV. The voltage-independent current reversed at the equilibrium potential for potassium ( E(K)), hence was carried by a K+ conductance, and was blocked by the selective KCNQ channel blockers XE991 and linopirdine. Similar results were obtained with KCNQ4 channels transiently transfected into Chinese hamster ovary cells (CHO). When (+/-)BMS-204352 was applied to stably expressed BK channels, only the voltage dependency was modulated. Retigabine, the classic activator of KCNQ channels, did not induce voltage-independent currents. Our data indicate that KCNQ4 channels may conduct voltage-dependent and voltage-independent currents in the presence of (+/-)BMS-204352.
AB - The compound BMS-204352 has been targeted for use against acute ischemic stroke, due to its activation of the large-conductance Ca2+-activated K-channel (BK). We have previously described that the racemate (+/-)BMS-204352 reversibly modulates KCNQ4 voltage dependency. Here we show that (+/-)BMS-204352 also induces a voltage-independent KCNQ4 current. The channels were stably expressed in human embryonic kidney cells (HEK293), and investigated by use of the whole-cell mode of the patch-clamp technique. (+/-)BMS-204352 was applied extracellularly (10 microM) in order to precipitate the robust appearance of the voltage-independent current. The voltage-independent KCNQ4 currents were recorded as instantaneous increases in currents upon hyperpolarizing or depolarizing voltage steps elicited from holding potentials of -90 or -110 mV. The voltage-independent current reversed at the equilibrium potential for potassium ( E(K)), hence was carried by a K+ conductance, and was blocked by the selective KCNQ channel blockers XE991 and linopirdine. Similar results were obtained with KCNQ4 channels transiently transfected into Chinese hamster ovary cells (CHO). When (+/-)BMS-204352 was applied to stably expressed BK channels, only the voltage dependency was modulated. Retigabine, the classic activator of KCNQ channels, did not induce voltage-independent currents. Our data indicate that KCNQ4 channels may conduct voltage-dependent and voltage-independent currents in the presence of (+/-)BMS-204352.
U2 - 10.1007/s00424-003-1116-x
DO - 10.1007/s00424-003-1116-x
M3 - Journal article
C2 - 12851819
VL - 446
SP - 607
EP - 616
JO - Pflügers Archiv - European Journal of Physiology
JF - Pflügers Archiv - European Journal of Physiology
SN - 0031-6768
IS - 5
ER -