Ion Channels and Respiratory Diseases
Did You Know: Ion Channels and their function in respiratory disease targets
The SARS-CoV-2 pandemic which emerged in late 2019, coupled with continued seasonal and pandemic influenza infections, has caused a significant problem for global public health and health systems worldwide. Antivirals and vaccines effective against these viruses are desperately needed in order to stem the pandemic and save lives.
A number of viroporins and ion channels are involved in viral infections and respiratory disorders, a selection is provided below.
Viroporins
Viroporins are potential drug targets for block of viral replication and the spread of infection.
Useful Reviews
Scott, C., & Griffin, S. 2015. Viroporins: structure, function and potential as antiviral targets. Journal of General VirologyNieva, J.L., Madan, V., Carrasco, L. 2012. Viroporins: structure and biological functions. Nature Reviews Microbiology.
Wang, K., Xie, S., Sun, B. 2011. Viral proteins function as ion channels. Biochim Biophys Acta Biomembr.
Viroporins of Sars-CoV
Sars-CoV 3a forms a potassium channel located on the surface of Sars-CoV infected cells and promotes virus release (Lu, W., et al., 2006). Additionally, the Sars-CoV 3a and E proteins have been shown to activate the NLRP3 inflammasome (Chen, I-Y., et al., 2019) and are involved in virus replication and pathogenesis (Castaño-Rodriguez et al, 2018).
Viroporins of Influenza virus
The M2 protein of influenza A is a proton-gated, proton selective ion channel that is essential for viral replication (Jalily, P.H., et al, 2020). Amantadine is a well-known blocker of the influenza A M2 proton channel, and has been used as an anti-influenza drug for many years. Unfortunately it is associated with a number of severe side effects and is no longer recommended for the treatment of influenza A due to resistance as a result of mutations in the M2 protein
Measuring viroporins
Viroporins can be measured using automated patch clamp when expressed in cell lines, or using the Orbit instruments when they are recombinantly expressed in bilayers.
Ca2+-release activated calcium channel (CRAC)
Useful Reviews
Staudermann, T.A. 2018. CRAC channels as targets for drug discovery and development. Cell Calcium
Measuring CRAC Channels
CRAC channels can be measured using automated patch clamp when expressed in cell lines, or using the Orbit instruments when they are recombinantly expressed in bilayers.
Volume-regulated anion channels (VRAC), LRRC8
Key Publications and Reviews
Zhou, C., Chen, X., Planells-Cases, R., et al. 2020. Transfer of cGAMP into Bystander Cells via LRRC8 Volume-Regulated Anion Channels Augments STING-Mediated Interferon Responses and Anti-viral Immunity. ImmunityStrange, K., Yamada, T., & Denton, G. 2019. A 30-year journey from volume-regulated anion currents to molecular structure of the LRRC8 channel. Journal of General Physiology
Measuring VRAC Channels
VRAC Channels can be measured using automated patch clamp when expressed in cell lines, or using the Orbit instruments when they are recombinantly expressed in bilayers.
VRAC Publications using Nanion Instruments
Two pore channels (TPC)
Key Publications
Sakurai, Y., Kolokoltsov, A.A., Chen, C-C., et al. 2015. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment. ScienceCastonguay, J., Orth, J.H.C., Müller, T., et al. 2017. The two-pore channel TPC1 is required for efcient protein processing through early and recycling endosomes. Nature Scientific Reports
Measuring Two Pore Channels
Two Pore Channels can be measured using automated patch clamp when expressed in cell lines, in lysosomes, or using the Orbit instruments when they are recombinantly expressed in bilayers.
Publications using Instruments from Nanion
Transporters - SLC6A19 in SARS-CoV-2
Key Publications
Yan, R., Zhang, Y., Li, Y., et al. 2020. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. ScienceMeasuring SLC19A and other Transporters
SLC19A can be measured using the SSM-electrophysiology technique. It may also be measured in bilayers if reconstituted and the effect of drugs acting on transporters can be measured using impedance.
TMEM16A
Key Publication
Danahay, H.L., Lilley, S., Fox, R., et al. 2019. TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis. American Journal of Respiratory and Critical Care MedicineMeasuring TMEM16A
TMEM16A Channels can be measured using automated patch clamp when expressed in cell lines, and can be activated using the internal perfusion feature of the SyncroPatch 384i or using the Orbit instruments when they are recombinantly expressed in bilayers.
Application Notes
P2X3 in chronic cough
Key Publications
Ford, A.P. & Undem, B.J. 2013. The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders. Frontiers in Cellular NeuroscienceFord, A.P. 2012. In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization. Purinergic Signalling
Measuring P2X3 Channels
P2X3 Channels can be measured using automated patch clamp when expressed in cell lines, or using the Orbit instruments when they are recombinantly expressed in bilayers.
Application Notes
Publications using Instruments from Nanion
CFTR
Useful Reviews
Noone, P.G. & Knowles, M.R. 2001. 'CFTR-opathies': disease phenotypes associated with cystic fibrosis transmembrane regulator gene mutations. Respiratory ResearchMall, M.A., & Hartl, D. 2014. CFTR: cystic fibrosis and beyond. European Respiratory Journal
Measuring CFTR Channels
CFTR Channels can be measured using automated patch clamp when expressed in cell lines, or using the Orbit instruments when they are recombinantly expressed in bilayers. The CFTR channel is an ABC transporter and can also be measured using the SSM-electrophysiology technique.