Potassium Channels, Renal Fibrosis, and Diabetes

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FIG. 1.
FIG. 1.

Diagram shows structure and function of a typical intermediate-/small-conductance KCa3.1 channel. A single subunit (out of four identical, forming a homotetramer) is depicted, with a pore region between transmembrane-spanning segments 5 and 6. A rise of cytosolic Ca2+, resulting from agonist-mediated release of inositol 1,4,5-trisphosphate or Ca2+ influx from plasma membrane channels (receptor-operated, voltage-operated, transient receptor potential) increases KCa3.1 open probability via constitutively bound calmodulin (calmodulin C-domain [C-CaM], calmodulin N-domain [N-CaM]), hyperpolarizing the cell. Subsequent Ca2+ influx creates a positive feedback, activating several signaling kinase cascades (extracellular signal–related kinase [ERK 1/2], p38-mitogen-activated protein kinase [MAPK], phosphatidylinositide 3 kinase [PI3K]/Akt, Smad2/3, mitogen-activated protein kinase, etc.). Further downstream events include expression of monocyte chemoattractant protein-1, intracellular adhesion molecule-1, plasminogen activator inhibitor, and several collagen isoforms, with resulting matrix deposition and fibrosis. Channel expression and/or surface translocation are controlled by kinases and transcription factors as well (upper left). AP-1, activator protein 1; RTK, receptor-tyrosine kinase.

This Article

  1. Diabetes vol. 62 no. 8 2648-2650
  1. Free via Open Access: OA