We have suggested that tubular flow triggers a mechano-sensory release of nucleotides and subsequent P2Y2 receptor-mediated [Ca2+ ]i signalling in mouse medullary thick ascending limb (JASN 16: 2005, 115A). Here we report that isolated perfused mTAL tubules from P2Y2 receptor wild type mice display a lively [Ca2+ ]i oscillatory behaviour. [Ca2+ ]i oscillations were visible in video-microscopy as spontaneous "blinking" (increases in fura-2 ratio or Fluo-4 intensity increases) randomly distributed in single cell areas over the entire length of the tubule (300mm). We found that [Ca2+ ]i oscillatory activity: 1. had a frequency of 0.12 Hz, 2. was reduced by > 65% in mTAL of P2Y2 KO mice, 3. the single oscillatory amplitude was significantly larger in P2Y2 receptor WT mice 4. was strictly dependent on physiological temperature (absent at 12oC) and 5. was strictly dependent on the presence of basolateral Ca2+ , 6. Scavenging of extracellular ATP with apyrase greatly reduced this activity by > 60%. These data show that mTAL displays a lively spontaneous [Ca2+ ]i oscillatory activity and our data strongly indicate that this is caused by spontaneous release of nucleotides and subsequent activation of P2 receptors. Thus, these results image the local auto- and paracrine signalling phenomenon of the renal tubule.