ATP-activated inward rectifier potassium channel activity

Definition

Target type: molecularfunction

Enables the transmembrane transfer of a potassium ion by an inwardly-rectifying voltage-gated channel, where the inward rectification is due to a voltage-dependent block of the channel pore by ATP. An inwardly rectifying current-voltage relation is one where at any given driving force the inward flow of K+ ions exceeds the outward flow for the opposite driving force. [GOC:cb, GOC:mah]

ATP-activated inward rectifier potassium channels (Kir channels) are a family of ion channels responsible for regulating potassium ion (K+) permeability across cell membranes. Their unique characteristic lies in their sensitivity to intracellular ATP, which acts as a direct regulator of channel activity.

When intracellular ATP levels are high, these channels are inhibited, preventing K+ efflux from the cell. Conversely, when ATP levels drop, the channels open, allowing K+ to flow out of the cell. This mechanism plays a crucial role in maintaining cellular homeostasis, particularly in response to energy stress.

The molecular mechanism of ATP-activated inward rectifier potassium channel activity involves a complex interplay of structural elements and their interactions with ATP.

The channel's structure consists of four transmembrane domains, which form a pore through the membrane. The pore is lined with amino acid residues that interact with K+ ions, allowing them to pass through the channel.

The ATP-binding site is located within the intracellular domain of the channel. This site is highly conserved across different Kir channel subtypes and is responsible for ATP's regulatory action.

When ATP binds to this site, it triggers a conformational change in the channel protein, leading to closure of the pore and inhibition of K+ permeability. This conformational change is thought to involve a direct interaction between ATP and the channel's cytosolic domain.

The specific mechanism by which ATP binding leads to channel closure remains an area of active research. However, studies have shown that ATP binding induces a change in the channel's gating properties, leading to a shift in the equilibrium between open and closed states. This shift favors the closed state, resulting in reduced K+ permeability.

The precise molecular events leading to this shift are still under investigation, but they are likely to involve a combination of factors, including:

- Direct interactions between ATP and specific amino acid residues within the ATP-binding site
- Conformational changes within the channel protein that propagate from the ATP-binding site to the pore region
- Changes in the interactions between the channel protein and other cellular components

The ATP sensitivity of Kir channels plays a critical role in regulating cellular function in various tissues and organs. For example, in the heart, these channels contribute to maintaining the resting membrane potential and regulating heart rate. In the brain, they are involved in neurotransmission and neuronal excitability. In the pancreas, they help regulate insulin secretion.

In addition to their role in normal cellular function, Kir channels are also implicated in various pathological conditions, including diabetes, heart disease, and neurological disorders.

Therefore, understanding the molecular mechanism of ATP-activated inward rectifier potassium channel activity is essential for developing new therapeutic strategies targeting these channels in various diseases.'
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Proteins (7)

Compounds (20)