What activates inactivation?
| العنوان: | What activates inactivation? |
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| المؤلفون: | Christopher A. Ahern |
| المصدر: | The Journal of General Physiology |
| بيانات النشر: | Rockefeller University Press, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Membrane potential, Voltage-gated ion channel, Physiology, Sodium channel, Sodium, chemistry.chemical_element, Cardiac action potential, Voltage-Gated Sodium Channels, Gating, Voltage-gated potassium channel, Membrane Potentials, chemistry, Anesthesia, Biophysics, Animals, Neural accommodation, Research Articles |
| الوصف: | Voltage-gated sodium channels are critical for the generation and propagation of electrical signals in most excitable cells. Activation of Na+ channels initiates an action potential, and fast inactivation facilitates repolarization of the membrane by the outward K+ current. Fast inactivation is also the main determinant of the refractory period between successive electrical impulses. Although the voltage sensor of domain IV (DIV) has been implicated in fast inactivation, it remains unclear whether the activation of DIV alone is sufficient for fast inactivation to occur. Here, we functionally neutralize each specific voltage sensor by mutating several critical arginines in the S4 segment to glutamines. We assess the individual role of each voltage-sensing domain in the voltage dependence and kinetics of fast inactivation upon its specific inhibition. We show that movement of the DIV voltage sensor is the rate-limiting step for both development and recovery from fast inactivation. Our data suggest that activation of the DIV voltage sensor alone is sufficient for fast inactivation to occur, and that activation of DIV before channel opening is the molecular mechanism for closed-state inactivation. We propose a kinetic model of sodium channel gating that can account for our major findings over a wide voltage range by postulating that DIV movement is both necessary and sufficient for fast inactivation. |
| تدمد: | 1540-7748 0022-1295 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::14f8db596a7a3f220c778d61ce339084Test https://doi.org/10.1085/jgp.201311046Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....14f8db596a7a3f220c778d61ce339084 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15407748 00221295 |
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