Two to Tango: The Calcium Pump

Two to Tango: The Calcium Pump

A molecular dance: Powered by ATP (near the red domain), calcium ions (yellow spheres) flow through this transport protein to generate huge chemical gradients, 10,000 times more concentrated on one side of the membrane than the other. As a result, when a signal arrives at the cell membrane, ion channels open and calcium ions can rush down their chemical gradient in waves (e.g., Intracellular Calcium Ion Flux of Tissue Engineered Cardiac Model). Calcium binds to sensor proteins which then signal a variety of events, ranging from muscle contraction, gene regulation, secretion of insulin, release of neurotransmitter, cell division and movement.

History: In 1883, Sidney Ringer was studying the contraction of isolated rat hearts suspended in a solution made from London tap water. The heart beat perfectly. When he replaced tap water with distilled water, it stopped. Ringer had serendipitously discovered that calcium in the ‘hard’ water was a critical messenger for muscle contraction, in a way that had nothing to do with its role in bones and teeth.

Family relations: The first ion pump of this type (P-type ATPase) was the sodium pump, discovered by Danish scientist Jens Skou in 1957, for which he won the Nobel prize. There are 36 variants in the human genome and they pump different ions such as calcium, protons, potassium and copper. They share a common mechanism in which the phosphate group of ATP becomes chemically attached to the pump protein in each cycle, transiently, to form a phosphoenzyme intermediate (hence the term, P-type).

Pumps in Medicine: The sodium pump is a target for cardiac glycosides (derived from foxgloves and milkweed) used in treating heart failure. The gastric proton pump is the target of blockbuster drugs used for controlling stomach acidity. (See: “Proton Pump Inhibitors” PPI animation for Perrigo Company) Calcium pumps are being tested in gene therapy and as targets for cancer.

Google+ Collaborations: ★ Many thanks to Kevin Staff ★ who generously donated his time to make this animated gif from this molecular simulation:

♫ Konstantin Makov suggests that you watch the Calcium Pump dance while listening to Libertango, because the ATPase reminds him of a couple dancing while being pierced with the arrow of amore (calcium!). Thank you Konstantin for the charming suggestion! ♫ Astor Piazzolla – Libertango

For #ScienceSunday hosted by Allison Sekuler and Robby Bowles .

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21 Responses to Two to Tango: The Calcium Pump

  1. Maya Posch says:

    I’m currently studying the workings of myosin in muscle tissue including the involvement of ATP to trigger the actual powerstrokes as part of a project to produce a non-organic alternative using polymers or similar. Molecular biochemistry has always been one of my favourite subjects 🙂

  2. Rajini Rao says:

    Very cool, Maya Posch ! Myosin motors are the workhorses of muscle contraction and we can learn a lot from them! You probably already know that calcium binds to troponin C which then moves out of the way to let myosin and actin interact and bring about muscle contraction.

  3. Once again WOWRajini Rao

  4. Maya Posch says:

    Rajini Rao Yeah… I get how it works, but finding an analogue in other structures as a replacement is tricky 🙂 As with everything in molecular chemistry, nothing ever truly happens the way you expect it to 🙂

    Having something which can bind to another structure when an intervening layer is temporarily removed, which then ‘pulls’ itself along that surface sounds easy enough, but it’s hard to replicate. I guess one could just take the easy way out and use the mRNA->protein route using existing cell structures, but that’s not how I roll 🙂

  5. Rajini Rao says:

    A worthy challenge..the artificial motor would have to cyclically bind and release the other material in response to a signal. Then they could be bundled together in fibers, just as in the muscle. Very thought provoking, thanks for sharing this Maya Posch .

  6. Maya Posch says:

    Rajini Rao I write about it on one of my blogs, the appropriately titled Jinzou Ningen/Artificial Human blog 🙂 Haven’t published much yet, but more articles are forthcoming 🙂

  7. Rajini Rao says:

    I hope you share the link to the blog post on G+, Maya. It would generate a lively discussion, I’m sure!

  8. Maya Posch says:

    Rajini Rao Once I publish my research & simulation results I’ll most definitely link to it 🙂 Haven’t worked much on it sadly due to my stressful personal situation… but still trying to complete this project.

    At any rate the link to said blog can be found via my G+ profile 🙂 Thank you for your interest 😀

  9. Gregory Esau says:

    Science and scientists rock! Thanks Rajini Rao and Maya Posch for your exchange here. Fascinating to say the least.

  10. Shiv Sankar says:

    that’s awesome ….:-))

  11. Great presentation. But I am still in love with SVCT pump 🙂

  12. Rajini Rao says:

    Miodrag Milić , sodium coupled Vitamin C interesting! Do you work on it? Of course, the energy source for Vitamin C (ascorbate) uptake is the sodium pump, close cousin of the calcium pump featured here. The electrochemical gradient of sodium ions drives the uptake of many nutrients, including Vit C.

  13. Yes, here is the list of other related transporters for those interested: including multivitamin transporter.

    Do I work on it ? Not by profession & yes, as a passion because it looks like C is primal panacea. Its interesting fact that organism up-regulates SVCT pumps on any stress which has clear practical consequence – if you tolerate lets say 2g vitamin C without laxative effect in normal state, in stress, particularly viral infection, you will tolerate 10-100x more. This happens in multiple sites in the body (for instance blood brain barrier starts to express SVCT2 after stroke only) and this holds for any animal out there. This transporter might be one of the most important out there – you die in-uterus without it and there is high number of SNPs in human population which correlates negatively to length of life.

  14. Rajini Rao says:

    LOL, Shah Auckburaully , PHDComics are always welcome..any time, any where 🙂 I hadn’t seen this accurate, I have to laugh and be embarrassed for my profession at the same time!

  15. Now that’s what I call molecular chemistry…

  16. Tom Lee says:

    Rajini Rao Another nice post, very educational and informative. Thanks!

  17. You make Science so real Rajini Rao and life like…connecting to the emotion…amazing is the word :))

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