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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.
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The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
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Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
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The resting membrane potential of a neuron (-70mV) is sustained due to the selective ion permeability of the membrane. At the resting potential, the membrane is slightly permeable to ions like sodium (Na+) and chloride (Cl−) and highly permeable to potassium ions (K+). Differences in the ions' concentration inside the cell compared to the outside are maintained by membrane transport proteins like channels and pumps.
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From Selective Permeation to Physiology in Potassium Channels.

Sun-Joo Lee1, Johanna Schillings2, Reinier de Vries2

  • 1Center for the Investigation of Membrane Excitability Diseases, and Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

Function (Oxford, England)
|October 31, 2025
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Potassium channels use a selectivity filter (SF) to allow potassium (K+) ions to pass while blocking sodium (Na+). Mutations in these channels disrupt ion flow, leading to various diseases.

Keywords:
monogenic diseasepermeationpotassium channelselectivity

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Physiology

Background:

  • Potassium channels are crucial for cellular electrical signaling.
  • The selectivity filter (SF) of potassium channels ensures high selectivity for K+ over Na+ (100-1000:1).
  • This selectivity arises from specific ion-binding sites within the SF that mimic aqueous ion coordination.

Purpose of the Study:

  • To review the biophysical and biochemical research detailing the atomic mechanisms of K+ channel selectivity and permeation.
  • To discuss the link between mutations in K+ channels and human diseases.
  • To emphasize the physiological and pathophysiological importance of K+ channel selectivity and permeation.

Main Methods:

  • Structural studies of K+ channels.
  • Computational simulations of ion permeation.
  • Biophysical analyses of channel function.
  • Biochemical investigations of channel components.

Main Results:

  • The K+ channel SF coordinates K+ ions through multiple binding sites, favoring K+ over Na+.
  • Ion conduction occurs via a "knock-on" mechanism, where ions push each other through the channel.
  • Mutations affecting K+ selectivity and permeation are implicated in various diseases.

Conclusions:

  • Understanding the atomic details of K+ channel SF is key to comprehending ion transport.
  • Dysfunctional K+ channels due to altered selectivity and permeation contribute to significant human pathologies.
  • Knowledge of these mechanisms is vital for physiologists and clinicians.