Molecular Mechanism of Gating in Cyclic Nucleotide-gated Ion Channels

 


  Launch in standalone player
 
Air date: Monday, January 28, 2008, 12:00:00 PM
Category: Neuroscience
Description: Cyclic nucleotide-regulated channels, such as CNG channels and HCN channels, underlie the primary electrical signals in phototransduction and olfactory transduction and control the repetitive firing activity of cardiac and neuronal cells. Activation of these channels involves the direct binding of cyclic nucleotide to an intracellular domain of the channel. Dr. Zagotta's lab has been interested in understanding the molecular mechanism for this allostery. To do this, they have employed a number of fluorescence approaches combined with patch-clamp fluorometry, a technique for simultaneously recording electrical current and fluorescence from excised inside-out patches. They explored the structure and conformational rearrangements of the C-terminal gating ring of the cyclic nucleotide-gated channel CNGA1 during activation by cyclic nucleotides. By monitoring fluorescent resonance energy transfer (FRET) between membrane-resident quenchers and fluorophores attached to the channel, Dr. Zagotta's lab detected no movement orthogonal to the membrane during channel activation. By monitoring FRET between fluorophores within the C-terminal region, they determined that the C-terminal end of the C-linker and the end of the C-helix move apart when channels open. They conclude that during channel activation, a portion of the gating ring moves parallel to the plasma membrane, hinging toward the central axis of the channel.

NIH Neuroscience Seminar Series
Author: William N. Zagotta, Ph.D., University of Washington
Runtime: 75 minutes
Download: Download Video
How to download a Videocast
CIT File ID: 14264
CIT Live ID: 6176
Permanent link: http://videocast.nih.gov/launch.asp?14264

 

Podcast information
Audio Podcasts   Video Podcasts
  Description Runtime     Description Runtime
Listen to the podcast Enhanced Audio Podcast 1:01:42   Watch the podcast Enhanced Video Podcast 1:01:42