Spontaneous electrical and Ca2+ signals in the mouse renal pelvis that drive pyeloureteric peristalsis

Summary 1. Peristalsis in the smooth muscle cell (SMC) wall of the pyeloureteric system is unique in physiology in that the primary pacemaker resides in a population of atypical SMCs situated near the border of the renal papilla. 2. Atypical SMCs display high-frequency Ca2+ transients upon the spontaneous release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)-dependent stores that trigger cation-selective spontaneous transient depolarizations (STDs). In the presence of nifedipine, these Ca2+ transients and STDs seldom propagate > 100 μm. Synchronization of STDs in neighbouring atypical SMCs into an electrical signal that can trigger action potential discharge and contraction in the typical SMC layer involves a coupled oscillator mechanism dependent on Ca2+ entry through L-type voltage-operated Ca2+ channels. 3. A population of spindle- or stellate-shaped cells, immunopositive for the tyrosine receptor kinase kit, is sparsely distributed throughout the pyeloureteric system. In addition, Ca2+ transients and action potentials of long duration occurring at low frequencies have been recorded in a population of fusiform cells, which we have termed interstitial cells of Cajal (ICC)-like cells. 4. The electrical and Ca2+ signals in ICC-like cells are abolished upon blockade of Ca2+ release from either IP3- or ryanodine-dependent Ca2+ stores. However, the spontaneous Ca2+ signals in atypical SMCs or ICC-like cells are little affected in W/W−v transgenic mice, which have extensive lesions of their intestinal ICC networks. 5. In summary, we have developed a model of pyeloureteric pacemaking in which atypical SMCs are indeed the primary pacemakers, but the function of ICC-like cells has yet to be determined.