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

Abstract

Migrating peristaltic contractions in the mammalian upper urinary tract serve to propel urine from the kidney through the ureter to the bladder, where it is stored until micturition. In most mammals, circumferencially cut strips of the renal pelvis display spontaneous contractions which decrease in frequency as strips are taken from regions more distal of the renal calyx, the isolated ureter being quiescent in most mammals except man and pig (Constantinou et al. 1978;Constantinou, 1979). Extracellular sucrose gap recordings from the guinea-pig renal pelvis indicated that the spontaneous contractions were associated with simple oscillations in the membrane potential, analogous to the 'pacemaker' action potentials recorded in the sino-atrial node of the mammalian heart. In contrast, electrically evoked contractions in both the distal renal pelvis and ureter were associated with action potentials consisting of a rapid rising phase and a long plateau (Zawalinski et al. 1975;Constantinou et al. 1979;Santicioli & Maggi, 1997). Thus, it has often been postulated that the initiation of peristaltic contractions in the upper urinary tract involves the spontaneous generation of 'pacemaker' potentials within the proximal renal pelvis which trigger 'driven' action potentials and contraction in the usually quiescent more distal regions of the upper urinary tract (

Pacemaker activity in the upper urinary tract

“…Klemm and associates (1999), using electron and confocal microscopy, identified 'atypical' smooth cells predominately at the pelvi-calyceal junction of the guinea pig upper urinary tract that fired 'pacemaker' potentials at a frequency higher than 'driven' action potentials recorded in 'typical' smooth muscle cells throughout the renal pelvis and ureter. These atypical smooth muscle cells, in contrast to typical smooth muscle cells, have less than 40% of their cellular area occupied by contractile filaments, and demonstrate sparse immunoreactivity for α-smooth muscle actin (Klemm et al, 1999;Lang et al, 2001). These atypical pacemaker cells are spindle shaped, 90-230 µm in length, and their electrical activity consists of simple waveforms with alternating depolarizing and repolarizing phases that occur at a relatively rapid frequency of 8-15/min.…”

Pacemakers in the upper urinary tract

“…Investigators have envisaged that autorhythmicity within the upper urinary tract involves a 'chain of coupled linear oscillators' with the most proximal oscillator firing at the highest frequency, The decreasing presence of 'atypical' SMC with distance from the papillate base has been correlated with the decreasing frequency of contraction. Atypical SMC have higher frequency (8-15 min-1) transient potentials of a simple waveform, those potentials are frequently (83% of cells) recorded in short "atypical" SMC (90-230μm in length) in the pelvi-calyceal junction of the guinea pig renal pelvis (Patacchini R et al 1998;Klemm MF et al 1999;Seki N et al 1990, Tsuchida S et al 1992. These transient potentials were recorded less frequently in the proximal renal pelvis (10% of recordings) and never in the ureter (Lang RJ et al 2001;Gosling JA & Dixon JS 1974).…”

“…They have been described as long thin cells, having a small nucleus and being irregularly-shaped due to the presence of many long branching processes. Their contractile myofilaments are arranged in bundles which are separated by large areas of cytoplasm containing Golgi cisternae, granular endoplasmic reticulum and small mitochondria occupying 3% of cell sectional area (Klemm MF et al 1999;Gosling JA & Dixon JS 1972) . They form areas of close apposition with each other and with typical SMC, these appositions being separated by long portions of naked membrane.…”

“…(Lang RJ et al 2001;Gosling JA & Dixon JS 1974) In multi-calyceal kidneys, 'atypical' SMC alone form the muscle coat of each minor calyx. A thin sheet of loosely-arranged atypical SMC extends between the minor calyces creating an open network near the point of attachment to the kidney (Gosling JA & Dixon JS 1972,1974Dixon JS & Gosling JA 1973,1982, the space between cells being filled with collagen-rich connective tissue and axon bundles (Lang RJ et al 2001;Klemm MF et al 1999;. A gradual thickening of the wall of the UUT of all mammals with distance from the pelvi-calyceal junction indicates the increasing presence of 'typical' SMC.…”

“…Intracellular microelectrode impalements have been made from the serosal surface of the pelvi-calyceal junction and renal pelvis of the guinea pig and it has been that 11-17% of cells fired spontaneous action potentials with a distinctive time course consisting of a single spike followed by a quiescent plateau and a rapid repolarization. (Klemm MF et al 1999).…”