6.9:
Non-gated Ion Channels
Ion channels are transmembrane proteins that allow the passive movement of ions to maintain the electrochemical gradient across the membrane.
These channels can be gated or non-gated. The gated ion channels require a stimulus, such as a ligand, voltage change, or mechanical stress, for their opening. Whereas, non-gated ion channels need no such stimulus.
Non-gated ion channels, also known as leak or passive channels, open and close at random, allowing ions to pass through whenever they open.
These channels have narrow, highly selective pores lined by conserved amino acid residues that allow the diffusion of only specific ions.
The potassium leak channels present on the nerve cell membrane are a well-studied example of non-gated ion channels. As the name suggests, these channels allow excess potassium ions to diffuse out of the cell down the concentration gradient.
This efflux of positive ions plays an important role in maintaining a negative charge on the cytoplasmic side and a positive charge on the exoplasmic side of the membrane – a characteristic of nerve cells when not conducting impulses.
6.9:
Non-gated Ion Channels
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism. This means no trigger is required for their opening and closing, hence the reference to leaking. There is no actual event that opens the channel; instead, it has an intrinsic rate of switching between the open and closed states. These channels are found throughout the neuron and contribute to the resting transmembrane voltage of the excitable membrane. For example, the potassium and sodium leak channels along with the sodium-potassium pump help maintain the neuron's resting membrane potential. The movement of the potassium ions down the electrochemical gradient via leakage channels creates a negative polarity inside the cell. This allows sodium ions to enter slowly through the sodium leak channels to prevent the neuron's membrane potential from constantly dropping lower than -70mV. At this level, the sodium-potassium pump will balance the concentration of sodium and potassium ions across the membrane.
Potassium leak channels like the two-pore domain potassium (K2P) family are widely distributed in the peripheral and central nervous systems, where they are targets for novel analgesic agents. When the activity of potassium leak channels decreases during inflammatory and neuropathic pain conditions, pain sensation is enhanced. Thus, drugs help activate these potassium leak channels to mitigate the pain.
Leitura Sugerida
- Lodish, Harvey, et al. Molecular Cell Biology. 8th ed. W.H. Freeman and Company, 2016.
- Alberts, Bruce, et al. Molecular Biology of the Cell. 6th ed. Garland Science, 2017.
- Openstax, Anatomy and Physiology, Section 12.4: The Action Potential
- Gada, Kirin, and Leigh D. Plant. "Two‐pore domain potassium channels: emerging targets for novel analgesic drugs: IUPHAR Review 26." British Journal of Pharmacology 176, no. 2 (2019): 256-266.