Tuesday, February 21, 2012

hERG: Legs, Drugs, and Heartbeats

The Whisky-a-Go-Go, 1965, Los Angeles
Credit: WFMU Ichiban Radio
Recently, while scribing my drug design post for CENtral Science, I happened to notice some abbreviations towards the back of a J. Med. Chemarticle. TNF - Tumor Necrosis Factor Alpha. (check). HCV - hepatitis C virus (check). hERG - human Ether-à-go-go Related Gene...


...what?!?


Yup. Biologists love a good play on words. Among the well-known Drosophila (fruit fly) genes are lush, sonic hedgehog, and methuselah*. In our bodies, certain drugs interact with the hERG receptor, one of several human homologues (close matches) to fly genes. But I hadn't realized that this PK point of conversation was named for a night club in L.A. 


Ever heard of a "go-go" dancer? 


Urban legend holds that famed club Whisky a Go-Go, a 1960s rock music hotbed, first institutionalized the profession when it opened on the Los Angeles Sunset Strip. To capitalize on a popular trend from New York and Paris, the owners set girls to "go-go" dancing in large cages suspended from the ceiling.


Not a Drosophila geneticist.
What's "go-go" dancing, you ask? Think of the female silhouettes you see before movies like James Bond, or better yet later spoof Austin Powers: International Man of Mystery - Tall boots, short skirts, and lots of hip shakes and leg twists. So, what does this have to do with fruit flies, or human drug testing?


As recounted in a 1991 Science News feature, neurogeneticist William Kaplan first noted the ether-à-go-go (eag) mutation in the 1960s. If these flies were knocked out with ether, their legs would twitch and shake, much like the famed dancers. When two researchers from the University of Wisconsin discovered similar mammalian genes, they took a page from the same book, naming them "erg," or "ether-à-go-go related genes."  



ECG of a single heartbeat
Source: Wikipedia Commons | Agateller


Warmke and Ganetsky, the two Wisconsin geneticists, found that the hERG gene encoded specific voltage-gated potassium channels in cell membranes (i.e., they open and close to allow potassium ions to flow out of the cell). In heart cells, these channels control the back-end of the heartbeat, the so-called "QT interval" (see graphic). When drugs block these channels, cardiac membrane repolarization (electrical charge balancing) takes longer, and a fatal arrhythmia may set in.


Seldane (terfenadine)
Anyone remember Seldane (terfenadine)? In the late 1980s, allergy sufferers praised it as a non-sedating antihistamine. However, it became a hERG poster child, and the FDA recommended its removal from the market in 1997. 


*Decoder ring: lush mediates alcohol response, sonic hedgehog (shh) controls organ and limb differentiation, and methuselah creates long-lived flies

16 comments:

  1. Irrespective of receiving daily oral or future injectable depot therapies, these require health care visits for medication and monitoring of safety and response. If patients are treated early enough, before a lot of immune system damage has occurred, life expectancy is close to normal, as long as they remain on successful treatment. However, when patients stop therapy, virus rebounds to high levels in most patients, sometimes associated with severe illness because i have gone through this and even an increased risk of death. The aim of “cure”is ongoing but i still do believe my government made millions of ARV drugs instead of finding a cure. for ongoing therapy and monitoring. ARV alone cannot cure HIV as among the cells that are infected are very long-living CD4 memory cells and possibly other cells that act as long-term reservoirs. HIV can hide in these cells without being detected by the body’s immune system. Therefore even when ART completely blocks subsequent rounds of infection of cells, reservoirs that have been infected before therapy initiation persist and from these reservoirs HIV rebounds if therapy is stopped. “Cure” could either mean an eradication cure, which means to completely rid the body of reservoir virus or a functional HIV cure, where HIV may remain in reservoir cells but rebound to high levels is prevented after therapy interruption.Dr Itua Herbal Medicine makes me believes there is a hope for people suffering from,Parkinson's disease,Schizophrenia,Lung Cancer,Breast Cancer,Colo-Rectal Cancer,Blood Cancer,Prostate Cancer,siva.Fatal Familial Insomnia Factor V Leiden Mutation ,Epilepsy Dupuytren's disease,Desmoplastic small-round-cell tumor Diabetes ,Coeliac disease,Creutzfeldt–Jakob disease,Cerebral Amyloid Angiopathy, Ataxia,Arthritis,Amyotrophic Lateral Scoliosis,Fibromyalgia,Fluoroquinolone Toxicity
    Syndrome Fibrodysplasia Ossificans ProgresSclerosis,Alzheimer's disease,Adrenocortical carcinoma.Asthma,Allergic diseases.Hiv_ Aids,Herpe ,Copd,Glaucoma., Cataracts,Macular degeneration,Cardiovascular disease,Lung disease.Enlarged prostate,Osteoporosis.Alzheimer's disease,
    Dementia.(measles, tetanus, whooping cough, tuberculosis, polio and diphtheria)
    Hpv,All Cancer Types,Diabetes,Hepatitis,I read about him online how he cure Tasha and Tara so i contacted him on drituaherbalcenter@gmail.com / info@drituaherbalcenter.com. even talked on whatsapps +2348149277967 believe me it was easy i drank his herbal medicine for two weeks and i was cured just like that isn't Dr Itua a wonder man? Yes he is! I thank him so much so i will advise if you are suffering from one of those diseases Pls do contact him he's a nice man.

    ReplyDelete

  2. Desert Safari Dubai provides a variety of all comprehensive packages for distinct types of desert safari, Our desert safari involve many varying options like dune buggies and quad bikes.

    desert safari dubai

    ReplyDelete
  3. We are leading exhibition stand designers and builders based in Qatar. We are involved in designing the exhibition booth and marketing display stalls for running trade fairs, marketing campaigns, promotional events, presentations in various qatar trade fairs.
    exhibition stand design companies in doha qatar

    ReplyDelete

  4. We are leading exhibition stand designers and builders based in GCC. We are involved in designing the exhibition booth and marketing display stalls for running trade fairs, marketing campaigns, promotional events, presentations in various GCC trade fairs.
    exhibition contractor

    ReplyDelete

  5. We are leading exhibition stand designers and builders based in GCC. We are involved in designing the exhibition booth and marketing display stalls for running trade fairs, marketing campaigns, promotional events, presentations in various GCC trade fairs.
    exhibition stand designers

    ReplyDelete

  6. We are leading exhibition stand designers and builders based in GCC. We are involved in designing the exhibition booth and marketing display stalls for running trade fairs, marketing campaigns, promotional events, presentations in various GCC trade fairs.
    stall fabricators

    ReplyDelete

  7. We are leading exhibition stand designers and builders based in GCC. We are involved in designing the exhibition booth and marketing display stalls for running trade fairs, marketing campaigns, promotional events, presentations in various GCC trade fairs.
    shell scheme stand builder

    ReplyDelete

  8. We are leading exhibition stand designers and builders based in abu-dhabi. We are involved in designing the exhibition booth and marketing display stalls for running trade fairs, marketing campaigns, promotional events, presentations in various abu-dhabi trade fairs.
    exhibition contractor in dubai

    ReplyDelete

  9. We are leading exhibition stand designers and builders based in Kuwait. We are involved in designing the exhibition booth and marketing display stalls for running trade fairs, marketing campaigns, promotional events, presentations in various Kuwait trade fairs.
    exhibition stand builder in kuwait

    ReplyDelete

  10. We are leading exhibition stand designers and builders based in Bahrain. We are involved in designing the exhibition booth and marketing display stalls for running trade fairs, marketing campaigns, promotional events, presentations in various bahrain trade fairs.
    exhibition contractor in bahrain

    ReplyDelete
  11. Our Exhibition stands can be fit into any space very easily, which allows our clients to create an impressive impression among their visitors.
    we build our stands to accommodate a maximum vertical space so that all the modules are placed at the same height. When it comes to arranging the modules, we create the best arrangements possible for you.
    We also arrange lighting and ventilation systems to ensure that the stands are safe and comfortable for visitors.
    exhibition stand contractors dubai

    ReplyDelete
  12. We are leading exhibition stand designers and builders based in Qatar. We are involved in designing the exhibition booth and marketing display stalls for running trade fairs, marketing campaigns, promotional events, presentations in various qatar trade fairs.
    exhibition stand contractors in doha qatar

    ReplyDelete
  13. Fantastic article. Your works are distinctive, easy to understand, and contain informative and inspiring material. Keep up the fantastic work

    ReplyDelete
  14. Prodigy Corporate Services is your dedicated partner for securing a General Trading License in Dubai, and our commitment to your success is unwavering"
    General Trading License In Dubai

    ReplyDelete