Identification of the cells underlying pacemaker activity in the guinea-pig upper urinary tract

1. The varying profile of cell types along the muscle wall of the guinea-pig upper urinary tract was examined electrophysiologically, using intracellular microelectrodes, and morphologically, using both electron and confocal microscopy. 2. Simple 'pacemaker' oscillations (frequency of 8 min(-1)) of the membrane potential were recorded in both the pelvi-calyceal junction (83% of cells) and the proximal renal pelvis (15% of cells), but never in the distal renal pelvis or ureter. When filled with the cell marker, neurobiotin, 'pacemaker' cells were spindle shaped and similar to 160 mu m in length. 3. In most cells of the ureter (100%) and in both the proximal (75%) and distal (89%) renal pelvis, spontaneous action potentials (frequency of 3-5 min(-1)) consisted of an initial spike, followed by a number of potential oscillations superimposed on a plateau phase. When filled with neurobiotin, cells firing these 'driven' action potentials, were spindle shaped and > 250 mu m in length. 4. Greater than 80 % of smooth muscle cells in the pelvi-calyceal junction were 'atypical', having < 40% of their sectional areas occupied by loosely packed contractile filaments. Most of the smooth muscle cells in the ureter (99.7%) and both the proximal (83%) and distal (97.5%) renal pelvis were of 'typical' appearance in that they contained cytoskeletal and contractile elements occupying > 60% of cross-sectional area. 5. 4 third type of spontaneously discharging cell fired 'intermediate' action potentials (3-4 min(-1)), consisting of a single spike followed by a quiescent plateau and an abrupt repolarization. These cells were morphologically similar to interstitial cells of Cajal (ICC). However, these 'ICC-like' cells were not immune-reactive for c-Kit, the proto-oncogene for tyrosine kinase. 6. In summary 'atypical' smooth muscle cells were predominant in the pelvi-calyceal junction and fired 'pacemaker' potentials at a frequency significantly higher than 'driven' action potentials recorded in 'typical' smooth muscle cells throughout the renal pelvis and ureter. 'Intermediate' action potentials were recorded in 'ICC-like' cells in both the pelvi-calyceal junction and renal pelvis. We suggest that these 'ICC-like' cells act as a preferential pathway, conducting and amplifying pacemaker signals to initiate action potential discharge in the driven areas of the upper urinary tract.