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

Richard J Lang, Hikaru Hashitani, Mary A Tonta, Justin L Bourke, Helena C Parkington, Hikaru Suzuki

Department of Physiology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia. rick.lang@med.monash.edu.au

Clinical and experimental pharmacology & physiology 2010 Apr

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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 Ca(2+) transients upon the spontaneous release of Ca(2+) from inositol 1,4,5-trisphosphate (IP(3))-dependent stores that trigger cation-selective spontaneous transient depolarizations (STDs). In the presence of nifedipine, these Ca(2+) transients and STDs seldom propagate > 100 mum. 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 Ca(2+) entry through L-type voltage-operated Ca(2+) 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, Ca(2+) 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 Ca(2+) signals in ICC-like cells are abolished upon blockade of Ca(2+) release from either IP(3)- or ryanodine-dependent Ca(2+) stores. However, the spontaneous Ca(2+) 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.

Citation

Richard J Lang, Hikaru Hashitani, Mary A Tonta, Justin L Bourke, Helena C Parkington, Hikaru Suzuki. Spontaneous electrical and Ca2+ signals in the mouse renal pelvis that drive pyeloureteric peristalsis. Clinical and experimental pharmacology & physiology. 2010 Apr;37(4):509-15