Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Biophysical Journal |
| Vol/bind | 92 |
| Udgave nummer | 8 |
| Sider (fra-til) | 2747-56 |
| Antal sider | 9 |
| ISSN | 0006-3495 |
| DOI | |
| Status | Udgivet - 2007 |
Bibliografisk note
Keywords: Animals; Cells, Cultured; Humans; Ion Channel Gating; KCNQ Potassium Channels; Membrane Potentials; Oocytes; Xenopus laevisAdgang til dokumentet
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I: Biophysical Journal, Bind 92, Nr. 8, 2007, s. 2747-56.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Inactivation as a new regulatory mechanism for neuronal Kv7 channels.
AU - Jensen, Henrik Sindal
AU - Grunnet, Morten
AU - Olesen, Søren-Peter
N1 - Keywords: Animals; Cells, Cultured; Humans; Ion Channel Gating; KCNQ Potassium Channels; Membrane Potentials; Oocytes; Xenopus laevis
PY - 2007
Y1 - 2007
N2 - Voltage-gated K(+) channels of the Kv7 (KCNQ) family have important physiological functions in both excitable and nonexcitable tissue. The family encompasses five genes encoding the channel subunits Kv7.1-5. Kv7.1 is found in epithelial and cardiac tissue. Kv7.2-5 channels are predominantly neuronal channels and are important for controlling excitability. Kv7.1 channels have been considered the only Kv7 channels to undergo inactivation upon depolarization. However, here we demonstrate that inactivation is also an intrinsic property of Kv7.4 and Kv7.5 channels, which inactivate to a larger extent than Kv7.1 channels at all potentials. We demonstrate that at least 30% of these channels are inactivated at physiologically relevant potentials. The onset of inactivation is voltage dependent and occurs on the order of seconds. Both time- and voltage-dependent recovery from inactivation was investigated for Kv7.4 channels. A time constant of 1.47 +/- 0.21 s and a voltage constant of 54.9 +/- 3.4 mV were determined. It was further demonstrated that heteromeric Kv7.3/Kv7.4 channels had inactivation properties different from homomeric Kv7.4 channels. Finally, the Kv7 channel activator BMS-204352 was in contrast to retigabine found to abolish inactivation of Kv7.4. In conclusion, this work demonstrates that inactivation is a key regulatory mechanism of Kv7.4 and Kv7.5 channels.
AB - Voltage-gated K(+) channels of the Kv7 (KCNQ) family have important physiological functions in both excitable and nonexcitable tissue. The family encompasses five genes encoding the channel subunits Kv7.1-5. Kv7.1 is found in epithelial and cardiac tissue. Kv7.2-5 channels are predominantly neuronal channels and are important for controlling excitability. Kv7.1 channels have been considered the only Kv7 channels to undergo inactivation upon depolarization. However, here we demonstrate that inactivation is also an intrinsic property of Kv7.4 and Kv7.5 channels, which inactivate to a larger extent than Kv7.1 channels at all potentials. We demonstrate that at least 30% of these channels are inactivated at physiologically relevant potentials. The onset of inactivation is voltage dependent and occurs on the order of seconds. Both time- and voltage-dependent recovery from inactivation was investigated for Kv7.4 channels. A time constant of 1.47 +/- 0.21 s and a voltage constant of 54.9 +/- 3.4 mV were determined. It was further demonstrated that heteromeric Kv7.3/Kv7.4 channels had inactivation properties different from homomeric Kv7.4 channels. Finally, the Kv7 channel activator BMS-204352 was in contrast to retigabine found to abolish inactivation of Kv7.4. In conclusion, this work demonstrates that inactivation is a key regulatory mechanism of Kv7.4 and Kv7.5 channels.
U2 - 10.1529/biophysj.106.101287
DO - 10.1529/biophysj.106.101287
M3 - Journal article
C2 - 17237198
SN - 0006-3495
VL - 92
SP - 2747
EP - 2756
JO - Biophysical Journal
JF - Biophysical Journal
IS - 8
ER -