Calcium wave of tubuloglomerular feedback

Am J Physiol Renal Physiol. 2006 Aug;291(2):F473-80. doi: 10.1152/ajprenal.00425.2005. Epub 2006 Feb 21.


ATP release from macula densa (MD) cells into the interstitium of the juxtaglomerular (JG) apparatus (JGA) is an integral component of the tubuloglomerular feedback (TGF) mechanism that controls the glomerular filtration rate. Because the cells of the JGA express a number of calcium-coupled purinergic receptors, these studies tested the hypothesis that TGF activation triggers a calcium wave that spreads from the MD toward distant cells of the JGA and glomerulus. Ratiometric calcium imaging of in vitro microperfused isolated JGA-glomerulus complex dissected from rabbits was performed with fluo-4/fura red and confocal fluorescence microscopy. Activation of TGF by increasing tubular flow rate at the MD rapidly produced a significant elevation in intracellular Ca(2+) concentration ([Ca(2+)](i)) in extraglomerular mesangial cells (by 187.6 +/- 45.1 nM) and JG renin granular cells (by 281.4 +/- 66.6 nM). Subsequently, cell-to-cell propagation of the calcium signal at a rate of 12.6 +/- 1.1 microm/s was observed upstream toward proximal segments of the afferent arteriole and adjacent glomeruli, as well as toward intraglomerular elements including the most distant podocytes (5.9 +/- 0.4 microm/s). The same calcium wave was observed in nonperfusing glomeruli, causing vasoconstriction and contractions of the glomerular tuft. Gap junction uncoupling, an ATP scavenger enzyme cocktail, and pharmacological inhibition of P(2) purinergic receptors, but not adenosine A(1) receptor blockade, abolished the changes in [Ca(2+)](i) and propagation of the calcium wave. These studies provided evidence that both gap junctional communication and extracellular ATP are integral components of the TGF calcium wave.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analysis
  • Adenosine Triphosphate / physiology
  • Animals
  • Arterioles / physiology
  • Calcium / analysis
  • Calcium / physiology*
  • Feedback / physiology*
  • Female
  • Gap Junctions / physiology
  • Juxtaglomerular Apparatus / blood supply
  • Juxtaglomerular Apparatus / chemistry
  • Juxtaglomerular Apparatus / physiology
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / chemistry
  • Kidney Glomerulus / physiology*
  • Kidney Tubules / blood supply
  • Kidney Tubules / chemistry
  • Kidney Tubules / physiology*
  • Rabbits
  • Receptor, Adenosine A1 / analysis
  • Receptor, Adenosine A1 / physiology
  • Receptors, Purinergic P2 / analysis
  • Receptors, Purinergic P2 / physiology
  • Signal Transduction / physiology
  • Time Factors
  • Vasoconstriction / physiology


  • Receptor, Adenosine A1
  • Receptors, Purinergic P2
  • Adenosine Triphosphate
  • Calcium