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Related Concept Videos

Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
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Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
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Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
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Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
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Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Non-gated Ion Channels01:24

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Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
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The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...

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Structural changes during HCN channel gating defined by high affinity metal bridges.

Daniel C H Kwan1, David L Prole, Gary Yellen

  • 1Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

The Journal of General Physiology
|August 30, 2012
PubMed
Summary

Hyperpolarization-activated cyclic nucleotide-sensitive nonselective cation (HCN) channels uniquely open upon hyperpolarization. Structural analysis reveals interactions between S4-S5 linkers and post-S6/C-linkers control HCN channel gating.

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Area of Science:

  • Molecular and Cellular Biology
  • Biophysics
  • Structural Biology

Background:

  • Hyperpolarization-activated cyclic nucleotide-sensitive nonselective cation (HCN) channels exhibit unique voltage-gated activation mechanisms.
  • The structural underpinnings of HCN channel unique gating remain largely unknown.
  • Previous studies suggest interactions between S4-S5 linker and post-S6/C-linker regions are crucial for HCN channel function.

Purpose of the Study:

  • To elucidate the structural basis for the unique hyperpolarization-dependent gating of HCN channels.
  • To investigate the spatial relationship and functional significance of interactions between the S4-S5 linker and post-S6/C-linker regions.
  • To propose a structural model for HCN channel voltage-dependent activation.

Main Methods:

  • Utilized a Cd(2+)-bridging scan by introducing paired cysteines into specific regions of the sea urchin HCN channel.
  • Constructed concatenated HCN channel subunits to examine inter-subunit interactions.
  • Developed a structural model based on experimental data to explain gating mechanisms.

Main Results:

  • High-affinity Cd(2+) bridges between S4-S5 linker and post-S6/C-linker induced either lock-open or lock-closed channel phenotypes.
  • These interactions are position-dependent, indicating distinct conformational states.
  • Interactions were observed between neighboring subunits, suggesting a quaternary structural role in gating.
  • Evidence suggests these regions interact in both open and closed states and move relative to each other during gating.

Conclusions:

  • The S4-S5 linker and post-S6/C-linker regions play a critical role in HCN channel gating through inter-subunit interactions.
  • A proposed model suggests voltage-sensor-driven movement of S4-S5 linkers rotates S5 helices, facilitating S6 helix movement and channel opening.
  • This mechanism provides insight into the unique voltage dependence of HCN channels.