Ion Channel Selectivity Assay

Ion channels are protein molecules widely present on cell membranes, providing energetically favorable channels for specific ions to pass through lipid membranes with the characteristics of passive diffusion permeability, extremely high transmission rate as well as ion selectivity. Selected ions can rapidly and passively enter or exit cells through ion channels according to their electrochemical gradients. This ionic activity generates transient dynamic potentials or maintain resting potentials, which greatly contributes to biofilm excitability and neural signaling processes. Several years of experience allowed Creative Biolabs to provide the most reliable and advanced ion channel selectivity assay services using various novel approaches.

Background of Ion Channel and Its Selectivity

The most typical and widely studied ion channels are K and Na channels. The process of cell membrane polarization and depolarization originates from the high basal permeability of K⁺ and selective permeability of K⁺ channels. However, Na⁺ channels, with their fast-gating kinetics as triggering elements to initiate action potentials, do not need to be as highly selective as K⁺ channels.

Fig 1. The full-length KcaA channel with its four subunits. (Roux, et al., 2011)

The most critical function of the voltage-gated potassium (Kv) channel is the selective permeability to K⁺ ions. In short, K⁺ ions can pass through the Kv channel more easily than Na⁺, which is extremely important for the recovery of the resting potential. Many theories about how ion channels are selective have been published. Although many claims use simple structural concepts to explain the mechanism of ion selectivity, more in-depth analysis shows that there is other kinetic and thermodynamic knowledge involved. The most intuitive explanation for the selectivity of ion channels is the concept of comfort matching. A rigid geometric position is reserved in the channel structure. A molecule of suitable size needs lower free energy to enter this structure, while a larger or smaller molecule encounters a larger energy barrier, and this difference in free energy is at the heart of ion channel selectivity.

Ion Channel Selectivity Profiling Assay

Disruption of ion channels on the surface of cell membranes associates with many serious diseases, including epilepsy, Alzheimer's disease, Parkinson's disease and a range of other neuroexcitatory diseases. The study of ion channels and their selectivity explains cell membrane permeability, selectivity, and channel gating mechanisms, laying the foundation for understanding cell excitatory activity and neural function. Moreover, ion channel selectivity profiling also helps to identify specificity and potential off-target effects.

Several approaches could be used to conduct ion channel testing. The structural/gene homology analysis of channel proteins has been utilized to determine the selectivity of the channel to a certain extent, and molecular dynamics simulations can simulate and calculate the energy required for a certain ion to pass through the channel according to the protein structure. Combined radiolabeled probes with ion channels to observe the state of ions across the membrane and potential off-target phenomena. The most thorough data for a rigorous assessment of ion channel activity are obtained by electrophysiology for functional assays, in addition to detecting interactions, the distribution of ions and the possible presence of agonists and antagonists can also be obtained.

Fig 2. Electrophysiological analysis of channel currents. (Obejero-Paz, et al., 2015)

Our Ion Channel Selectivity Assays

At Creative Biolabs, we provide validated and stable testing services for ion channel selectivity profiling assays, we can screen and classify your channels, provide stable cell lines, detect on-target and off-target effects, and contribute to your electrophysiology and immunology research. Please contact us for further information.

References

1. Roux, B.; et al. Ion selectivity in channels and transporters. Journal of General Physiology. 2011, 137(5): 415-426.
2. Obejero-Paz, C.A.; et al. Quantitative profiling of the effects of vanoxerine on human cardiac ion channels and its application to cardiac risk. Scientific Reports. 2015, 5: 17623.