The intact mouse nephron (mTAL) displays flow-induced increases in [Ca²⁺]_i, a function which is greatly reduced in mice deplete of the major purinerigic receptor in this segment (P2Y2). We therefore suggested that tubular flow triggers a mechano-sensory release of nucleotides and subsequent P2Y2 receptor-mediated [Ca²⁺]_i signalling (JASN 16: 2005, 115A). Here we report that isolated perfused mTAL tubules from wild-type mice display a lively [Ca²⁺]_i oscillatory behaviour. [Ca²⁺]_i oscillations were visible as spontaneous "blinking" (increase in fura-2 ratio) randomly distributed over the tubule. Spontaneous, transient [Ca²⁺]_i increases (events) above a chosen threshold of >0.1 ratio units were measured in multiple ROIs ( 20 x 25 mm) over the entire tubule. In total, 1036 events with a mean frequency of one/6.2 min were measured in P2Y2 WT mice (n=18). The mean amplitude and duration of the events was 0.27+/-0.01 ratio units and 42.2+/-1.3 s, respectively. In sharp contrast spontaneous [Ca²⁺]_i oscillation were nearly absent in P2Y2 KO mice. Only 138 events with a mean frequency of one/31.3 min were measured. Their amplitude was reduced to 0.15+/-0.01 with no change in their duration (42.5+/-2.9 s)(n=11). These data show that spontaneous [Ca²⁺]_i oscillations in mouse mTAL require luminal and/or basolateral P2Y2 receptors and further support a mechanically stimulated, flow-dependent release of nucleotides and subsequent activation of P2-receptors.