Related Experiment Video
Updated: Mar 31, 2026
Pull-down of Calmodulin-binding Proteins
Published on: January 23, 2012
Ca(2+)/calmodulin regulates Kvβ1.1-mediated inactivation of voltage-gated K(+) channels
Sandip M Swain1, Nirakar Sahoo1, Sophie Dennhardt1
1Center for Molecular Biomedicine, Department of Biophysics, Friedrich Schiller University Jena &Jena University Hospital, Hans-Knöll-Str. 2, D-07745 Jena, Germany.
Abstract:
A-type K(+) channels open on membrane depolarization and undergo subsequent rapid inactivation such that they are ideally suited for fine-tuning the electrical signaling in neurons and muscle cells. Channel inactivation mostly follows the so-called ball-and-chain mechanism, in which the N-terminal structures of either the K(+) channel's α or β subunits occlude the channel pore entry facing the cytosol. Inactivation of Kv1.1 and Kv1.4 channels induced by Kvβ1.1 subunits is profoundly decelerated in response to a rise in the intracellular Ca(2+) concentration, thus making the affected channel complexes negative feedback regulators to limit neuronal overexcitation. With electrophysiological and biochemical experiments we show that the Ca(2+) dependence is gained by binding of calmodulin to the "chain" segment of Kvβ1.1 thereby compromising the mobility of the inactivation particle. Furthermore, inactivation regulation via Ca(2+)/calmodulin does not interfere with the β subunit's enzymatic activity as an NADPH-dependent oxidoreductase, thus rendering the Kvβ1.1 subunit a multifunctional receptor that integrates cytosolic signals to be transduced to altered electrical cellular activity.
Insights
Calcium ions slow the inactivation of A-type potassium channels by binding calmodulin to Kvβ1.1 subunits. This mechanism helps regulate neuronal excitability and integrates cellular signals.
Area of Science:
- Neuroscience
- Molecular Biology
- Biophysics
Background:
- A-type K(+) channels are crucial for electrical signaling in neurons and muscle cells.
- Channel inactivation, often via the ball-and-chain mechanism, regulates channel function.
- Kvβ1.1 subunits mediate inactivation of Kv1.1 and Kv1.4 channels.
Purpose of the Study:
- To investigate the mechanism by which intracellular calcium concentration affects Kv1.1/Kvβ1.1 channel inactivation.
- To elucidate the role of calmodulin in calcium-dependent regulation of channel inactivation.
- To determine if calcium/calmodulin interaction affects the enzymatic activity of Kvβ1.1.
Main Methods:
- Electrophysiological recordings to measure channel activity and inactivation kinetics.
- Biochemical assays to confirm protein interactions and enzymatic activity.
- Mutational analysis to identify key binding sites.
Main Results:
- Intracellular Ca(2+) profoundly decelerates Kv1.1 and Kv1.4 channel inactivation mediated by Kvβ1.1 subunits.
- Calmodulin binds to the 'chain' segment of Kvβ1.1, hindering the mobility of the inactivation particle.
- Ca(2+)/calmodulin binding does not interfere with the oxidoreductase enzymatic activity of Kvβ1.1.
Conclusions:
- Kvβ1.1 subunits act as multifunctional receptors, integrating cytosolic Ca(2+) signals.
- Calmodulin mediates the calcium-dependent regulation of A-type channel inactivation.
- This regulatory mechanism allows Kvβ1.1 to fine-tune neuronal electrical activity and limit overexcitation.
Related Concept Videos
01:16Calmodulin-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,...
01:26Voltage-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 types of...
01:26Voltage-gated Ion Channels
01:19The 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....
01:18Antihypertensive Drugs: Action of Calcium Channel Blockers
01:27Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...