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

• Published in: The Journal of physiology 1999-09, Vol.519 (3), p.867-884
• Main Authors: Klemm, Megan F., Exintaris, Betty, Lang, R. J.
• Format: Article
• Language: English
• Subjects: Action Potentials; Animals; Biotin - analogs & derivatives; Biotin - analysis; Cell Communication; Electrophysiology; Epithelial Cells - physiology; Guinea Pigs; Microscopy, Confocal; Muscle, Smooth - cytology; Original; Urinary Tract - cytology; Urinary Tract - innervation
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.1999.0867n.x

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. 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 ≈160 μm in length. 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 μm in length. 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. 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. 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.