negative regulation of delayed rectifier potassium channel activity

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of delayed rectifier potassium channel activity. [GOC:BHF, GOC:mtg_cardiac_conduct_nov11, GOC:rl, GOC:TermGenie, PMID:11299204]

Negative regulation of delayed rectifier potassium channel activity is a critical process in controlling the excitability of cells, particularly in the nervous system and heart. Delayed rectifier potassium channels (K(V) channels) are responsible for the repolarization phase of the action potential, ensuring that the cell returns to its resting state after depolarization. Negative regulation of this activity involves mechanisms that suppress or decrease the activity of these channels, thereby influencing the duration and frequency of action potentials.

Here's a detailed description of the process:

1. **Channel Gating and Conformation:** K(V) channels are multimeric proteins with four subunits, each containing a pore-forming region and voltage-sensing domains. These channels exhibit a characteristic "delayed rectification" behavior, meaning they open slowly after depolarization and remain open for an extended period, contributing to repolarization.
2. **Inhibition by Ligands:** Various ligands can interact with K(V) channels and inhibit their activity. These ligands can be intracellular or extracellular and may bind to specific sites on the channel protein.
* **Internal Blockers:** Intracellular molecules such as intracellular calcium or certain signaling molecules can bind to the pore region or other parts of the channel, physically blocking the flow of potassium ions.
* **Extracellular Blockers:** Extracellular toxins or drugs can bind to the external surface of the channel, interfering with its activation or deactivation.
3. **Phosphorylation and Deactivation:** Protein kinases can phosphorylate specific amino acids on the K(V) channel proteins, leading to conformational changes that alter their activity. Phosphorylation can either inhibit or enhance channel activity depending on the specific site and kinase involved.
4. **Interaction with Other Proteins:** K(V) channels can interact with other proteins that regulate their activity. For example, chaperone proteins can assist in folding and trafficking the channels to the plasma membrane, while scaffolding proteins can anchor them to specific locations.
5. **Channel Trafficking and Expression:** The number of K(V) channels at the cell surface can be regulated by various mechanisms. Changes in the rate of channel synthesis, degradation, or trafficking can influence the overall channel density and activity.
6. **Alterations in Membrane Properties:** Changes in the lipid composition of the cell membrane can impact the activity of K(V) channels. Membrane fluidity, cholesterol content, and other factors can influence channel gating and function.

Negative regulation of delayed rectifier potassium channels plays a critical role in maintaining cellular homeostasis, modulating excitability, and influencing the duration and timing of action potentials. Dysregulation of these channels is linked to various physiological conditions, including cardiovascular disorders, neurological diseases, and certain types of cancer. Therefore, understanding the mechanisms of negative regulation of these channels is crucial for developing therapeutic interventions for these conditions.'
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Proteins (1)

Compounds (38)