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: http://www.pumpkin.au.dk/research/download-gallery/
♫ 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 .