K Channels

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Potassium is obviously a key ion in nephrologists’ constant battle against reduced renal clearance. What about the potassium channels which are responsible for the trafficking of this ion in & out of the cell?

There is a marked diversity of K channels–amazingly, there are over 80 different K channel genes in the human genome? Although there are many different types of K channels categorized based on their mechanism (e.g., calcium-activated K channels; inwardly-rectifying K channels; voltage-gated K channels; tandem pore domain K channels), they all contain the same basic structure, consisting of 4 identical or near-identical subunits forming a tetramer with a central ion conducting pore. The Chemistry Nobel Prize for discovering the structure of K channels was given to Rod McKinnon in 2003.

It’s also important to make the distinction between CHANNELS and TRANSPORTERS, both of which are important in the kidney. CHANNELS are pores which allow a very rapid transport of ions into or out of the cell following an electochemical gradient. An example of a potassium channel in the nephron is the ROMK channel, found in the thick ascending limb. This channel allows a “backleak” of K+ ions taken into the cell which is important for maintaining the negative intracellular potential at about -70mV. In contrast TRANSPORTERS involve the binding of specific ions, often in a precise stoichiometry, which shuttles these ions either with or against their concentration gradient. Not surprisingly, ions move across the membrane much slower with transporters than with channels, but transporters offer the advantage of being able to transport against a concentration gradient and by regulating the correct ratio of ions. An example of an important renal K transporter (there are many) is the Na/K/2Cl cotransporter, also in the thick ascending limb.

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