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

Abstract

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.

The pelvis–kidney junction contains HCN3, a hyperpolarization-activated cation channel that triggers ureter peristalsis

“…Further characterization of both atypical and HCN-positive cell types in the upper urinary tract will determine whether they are in fact the same cell population. 47 Alternatively, it is possible that HCN channel activity indirectly triggers smooth-muscle contractions at the PKJ. For example, HCN channel activity may be important for release of prostaglandins that support urinary tract peristalsis.…”

Interstitial Cells of Cajal in the Urinary Tract

“…Again, the ASMC were found to be the main pacemakers, whereas the ICC had more of a supportive role, firing less frequent Ca 2+ -transients, and long duration action potentials (Lang et al 2007a and b). Spontaneous Ca 2+ signals in ICC were sensitive to blockade of Ca 2+ release from IP3 or ryanodine-dependent intracellular stores (Lang et al 2010). Study of W/Wv transgenic mice unfortunately showed no change in ICC Ca 2+ -signaling (Lang et al 2009), suggesting that the renal pelvis, like the urinary bladder, is not significantly affected by the c-Kit mutation ).…”

Calcium Signaling in Interstitial Cells: Focus on Telocytes

“…The ICCs and ICLCs are considered as electrical pacemaker cells and this role was documented for some organs like gastrointestinal tract, urinary tract and male genital organs [63,69,70]. It is also considered that ICLCs might intermediate the signal transduction between nervous and muscle cells [71].…”

“…As an important issue, these Ca 2+ signals present ubiquitous temporal characteristics depending on species and tissues and have greater amplitude but lower frequency in comparison with the signals in the neighboring smooth muscle cells [70]. …”