Related Experiment Video
Updated: Jun 15, 2025

Patch Clamp and Perfusion Techniques for Studying Ion Channels Expressed in Xenopus oocytes
Published on: January 10, 2011
Structural basis for the subtype-selectivity of KCa2.2 channel activators
Miao Zhang1, Young-Woo Nam1, Alena Ramanishka1
1Chapman University.
None:
Small-conductance (KCa2.2) and intermediate-conductance (KCa3.1) Ca2+-activated K+ channels are gated by a Ca2+-calmodulin dependent mechanism. NS309 potentiates the activity of both KCa2.2 and KCa3.1, while rimtuzalcap selectively activates KCa2.2. Rimtuzalcap has been used in clinical trials for the treatment of spinocerebellar ataxia and essential tremor. We report cryo-electron microscopy structures of KCa2.2 channels bound with NS309 and rimtuzalcap, in addition to KCa3.1 channels with NS309. The different conformations of calmodulin and the cytoplasmic HC helices in the two channels underlie the subtype-selectivity of rimtuzalcap for KCa2.2. Calmodulin's N-lobes in the KCa2.2 structure are far apart and undergo conformational changes to accommodate either NS309 or rimtuzalcap. Calmodulin's Nlobes in the KCa3.1 structure are closer to each other and are constrained by the HC helices of KCa3.1, which allows binding of NS309 but not of the bulkier rimtuzalcap. These structures provide a framework for structure-based drug design targeting KCa2.2 channels.
Related Concept Videos
Voltage-gated Ion Channels
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Role of Ion Channels in Neuronal Computation
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
Ligand-gated Ion Channels
Three Subfamilies of Ligand-gated Ion Channels
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...
Non-gated Ion Channels
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....

