geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Proton block of the pore underlies the inhibition of hERG cardiac K+ channels during acidosis


, : Proton block of the pore underlies the inhibition of hERG cardiac K+ channels during acidosis. American Journal of Physiology. Cell Physiology 302(12): C1797-C1806

Human ether-a-go-go-related gene (hERG) potassium channels are critical determinants of cardiac repolarization. Loss of function of hERG channels is associated with Long QT Syndrome, arrhythmia, and sudden death. Acidosis occurring as a result of myocardial ischemia inhibits hERG channel function and may cause a predisposition to arrhythmias. Acidic pH inhibits hERG channel maximal conductance and accelerates deactivation, likely by different mechanisms. The mechanism underlying the loss of conductance has not been demonstrated and is the focus of the present study. The data presented demonstrate that, unlike in other voltage-gated potassium (Kv) channels, substitution of individual histidine residues did not abolish the pH dependence of hERG channel conductance. Abolition of inactivation, by the mutation S62T, also did not affect the proton sensitivity of channel conductance. Instead, voltage-dependent channel inhibition ( = .18) indicative of pore block was observed. Consistent with a fast block of the pore, hERG S62T single channel data showed an apparent reduction of the single channel current amplitude at low pH. Furthermore, the effect of protons was relieved by elevating external K+ or Na+ and could be modified by charge introduction within the outer pore. Taken together, these data strongly suggest that extracellular protons inhibit hERG maximal conductance by blocking the external channel pore.

US$19.90

PMID: 22517356

DOI: 10.1152/ajpcell.00324.2011


Other references

Bosch-Barrera, J.; García-Franco, C.; Guillén-Grima, F.; Moreno-Jiménez, M.; López-Picazo, Jé.María.; Gúrpide, A.; Pérez-Gracia, Jé.Luis.; Aristu, J.; Torre, W.; García-Foncillas, Jús.; Gil-Bazo, I., 2013: The multimodal management of locally advanced N2 non-small cell lung cancer: is there a role for surgical resection? A single institution's experience. The management of operable locally advanced N2 non-small cell lung cancer (NSCLC) is a controversial topic. Concurrent chemoradiation (CT-RT) is considered the standard of care for inoperable or unresectable patients, but the role of trimodality t...

Bondarenko, A.S.; Bakina, L.A.; Kleĭner, E.M.; Sheĭchenko, V.I.; Gil'zin, M.A.; Khokhlov, A.S.; Poddubnaia, N.M.; Skorobogat'ko, T.I., 1968: Biological properties and chemical nature of the antibiotic from Bidens cernuus L. Antibiotiki 13(2): 167-171

Chen, Y-Fang.; Wang, D-Ni.; Chen, Z-Ting.; Zhao, Z-Hua.; Lin, Y.; Wang, H-Yan.; Wang, N., 2016: Risk factors associated with acute/subacute cerebral infarction in HIV-negative patients with cryptococcal meningitis. To explore the risk factors associated with acute/subacute cerebral infarction (ASCI) in HIV-negative patients with cryptococcal meningitis (CM). This case-control study included 10 HIV-negative CM patients with ASCI and 30 age- and sex-matched HI...

Szomolay, B.; van den Berg, H.A., 2015: Modulation of T-cell receptor functional sensitivity via the opposing actions of protein tyrosine kinases and phosphatases: a mathematical model. Combining receptor kinetics and stochastic modelling of receptor activation, we show that a T-cell can specifically augment its functional sensitivity to one particular peptide ligand while simultaneously decreasing its sensitivity to other ligand...

Palmer, R.F.; Espino, D.V.; Dergance, J.M.; Becho, J.; Markides, K., 2013: The role of physical activity and diabetes status as a moderator: functional disability among older Mexican Americans. we investigate the temporal association between the rate of change in physical function and the rate of change in disability across four comparison groups: Those with and without diabetes who report >30 min of physical activity per day, and tho...

Uslu, M.M.; Bozdogan, O.; Güney, S.; Bilgili, H.; Kaya, U.; Olcay, B.; Korkusuz, F., 1999: The effect of extracorporeal shock wave treatment (ESWT) on bone defects. An experimental study. The aim of this study was to investigate the effects of extracorporeal shock wave therapy (ESWT) on the formation of callus in bone defects created in rabbit radii. this study searches for an answer to whether ESWT may have a therapeutic effect on...

Láng, G.G.; Horányi, Görgy., 2006: Comment on "Role of the anion in the underpotential deposition of cadmium on a Rh(111) electrode: probed by voltammetry and in situ scanning tunneling microscopy". Journal of Physical Chemistry. B 110(7): 3444-3446

Ando, T.; Komaki, G.; Karibe, M.; Kawamura, N.; Hara, S.; Takii, M.; Naruo, T.; Kurokawa, N.; Takei, M.; Tatsuta, N.; Ohba, M.; Nozoe, S.; Kubo, C.; Ishikawa, T., 2001: 5-HT2A promoter polymorphism is not associated with anorexia nervosa in Japanese patients. Genetic factors have been implicated in playing a significant role in susceptibility to anorexia nervosa (AN). Among many candidate genes for AN, an association with the A allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A re...

Kool, M.B.; van Middendorp, H.; Bijlsma, J.W.J.; Geenen, R., 2012: Patient and spouse appraisals of health status in rheumatoid arthritis and fibromyalgia: discrepancies and associations with invalidation. The health problems of patients with rheumatoid arthritis and fibromyalgia are mostly invisible to others, which can lead to a discrepancy between patients' and spouses' appraisals of the severity of the health problems. As a consequence...

Nakano, H.; Shinohara, K., 1993: Comparison of X-ray induced cell death between the two subclones of MOLT-4. Journal of Radiation Research 34(4): 365