1. Peristalsis in the mammalian upper urinary tract (UUT) is mostly myogenic in origin, originating predominately in the proximal pelvicalyceal regions of the renal pelvis, an area that is enriched with specialized smooth muscle cells termed 'atypical' smooth muscle cells. Propagating peristaltic contractions are little affected by blockers of either autonomic nerve function or nerve impulse propagation; however, blockers of sensory nerve function or prostaglandin synthesis reduce both the frequency and the strength of the spontaneous contractions underlying peristalsis. 2. The electrical drive for these peristaltic contractions has long been considered to involve mechanisms analogous to the heart, such that 'atypical' smooth muscle cells generate spontaneous 'pacemaker' action potentials. These pacemaker potentials trigger the firing of action potentials and contraction in the muscular regions of the renal pelvis, which propagate distally to the ureter, propelling urine towards the bladder. 3. Recent intracellular microelectrode and single cell/channel patch-clamp studies have revealed that the ionic conductances underlying the action potentials recorded in the UUT are likely to involve the opening and slow closure of voltage-activated 'L-type' Ca2+ channels, offset by the time-dependent opening and closure of both voltage- and Ca(2+)-activated K+ channels. 4. In the present review we summarize the current knowledge of the ionic mechanisms underlying action potential discharge in the UUT, as well as present our view on how this electrical activity supports the initiation and conduction of UUT peristalsis.

1 The eects of circumferentially-applied stretch on the spontaneous contractility of a whole mount preparation of the guinea-pig upper urinary tract (UUT) (renal pelvis and ureter) were investigated by use of standard isometric tension recording techniques. 2 Simultaneous tension recordings of the proximal and distal portions of the renal pelvis (RP) and ureter revealed that spontaneous contractions, in 79% (n=66) of preparations, originated in the proximal RP (at a frequency of 4.5 min 71 ) and propagated to the distal RP and ureter at a velocity of 1 ± 3 cm s 71. Pretreatment with tetrodotoxin (TTX) (3 ± 10 mM) or N G -nitro-L-arginine (100 mM) had little eect on the spontaneous contractility of the UUT, motility indexes (MIs) (contraction amplitude6contraction frequency) calculated after 20 min exposure were little aected by TTX or N G -nitro-L-arginine (L-NOARG). o-Conotoxin GVIA (100 nM) signi®cantly reduced MI values in both the proximal RP and ureter. 3 Exposure of the spontaneously-active UUT to capsaicin (10 mM for 15 min) induced a transient increase in UUT contractility, followed by a prolonged negative inotropic eect. The MI values, calculated 60 min after the washout of capsaicin, for the proximal and distal RP and ureter were reduced to 56%, 53% (n=18) and 61% (n=16), respectively, of their control values. This capsaicin pretreatment blocked the positive inotropic eects of transmural electrical nerve stimulation on UUT contractility to reveal a small inhibitory eect which was readily blocked by tetrodotoxin (3 mM) (n=3). The excitatory and inhibitory actions of nerve stimulation were both blocked by TTX (3 mM) 4 A second exposure to capsaicin (10 mM for 15 min), further reduced the MI values (calculated 60 min after washout) in the proximal and distal RP to 41% and 31%, respectively (n=6; P50.05), of the initial control values. 5 In 61% (n=99) of preparations, the application of stretch to the proximal RP (0.5 to 2 mm) evoked a decrease in the amplitude of the contractions recorded in the distal RP, but not in the ureter. Stretch applied to the distal RP or ureter had no eect on the contractions recorded in the other regions of the UUT. 6 In 5 out of 6 preparations, a single application of capsaicin (10 mM for 15 min) had little eect on the change in contractile force of the distal RP evoked upon stretch of the proximal RP. 7. The inhibition of the distal RP upon stretch of the proximal RP was partially reduced (P50.05) when the UUT was pretreated with the calcitonin gene-related peptide (CGRP) receptor antagonist, hCGRP (8 ± 37) (1 mM). 8. The application of the CGRP receptor agonist, hCGRP (100 nM) inhibited contractility in the UUT in a region dependent manner. The MI of the proximal RP was decreased 32% after 6 min; while the MIs of the distal RP and ureter were reduced 83% and 63%, respectively, within 5 min of the application of hCGRP. 9. Glibenclamide (1 mM) had little eect on the spontaneous contractility of the UUT, but signi®cantly reduced the inhibition of the distal RP evoked upon stret...