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 approximately 160 microm 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 microm 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. A 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 immuno-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.