Morphology, Calcium Signaling and Mechanical Activity in Human Ureter

Abstract

To our knowledge this study represents the first measurements of Ca signals in the human ureter obtained during phasic contractions and in response to agonists. Results show that it is controlled by fast propagating Ca waves, which spread rapidly between the muscle bundles, producing regular contractions, and drugs that interfere with excitability or Ca entry through L-type Ca channels have profound effects on Ca signaling and contractility. These data are discussed in relation to the treatment of patients with suspected ureteral dysfunction using Ca entry blockers.

Modulation of ureteric Ca signaling and contractility in humans and rats by uropathogenic E. coli

“…This is consistent with our earlier findings concerning the characteristics of Ca signaling and contractility in human ureter (13). Although our sample number is limited in size, the responses to UPEC were consistent and seen in all tissues.…”

“…Ureteric cell membrane excitability is also regulated by calcium-activated K channels (KCa) and Cl channels (8,33,35). The human ureter has been less well-studied but we recently characterized Ca signaling and ion channel expression (13). However, as mentioned above, there are little or no data concerning how these mechanisms are affected by UPEC.…”

Escherichia coli-Mediated Impairment of Ureteric Contractility Is Uropathogenic E. coli Specific

“…For measurements of intracellular calcium, Indo-1 was used as described elsewhere [3, 34]. Loaded ureteric preparations were mounted on 2 stainless steel hooks, one of which was attached to a force transducer, and stretched (passive force being 25%–30% of the active force produced by electrical field stimulation to set optimal length, as spontaneous activity was rarely seen in these preparations).…”

“…As the ureters perform an essential function in the transportation of urine from the kidneys to the bladder, efficient ureteric contractility and peristalsis is vital in preventing renal infection. Peristalsis is brought about by propagating action potentials giving rise to global Ca transients, which underlie waves of phasic contractions of the smooth muscle that pass down the ureteric walls [3]. It has been shown that E. coli colonization can impair ureteric peristalsis, which in turn potentiates the infection due to urinary stasis and/or vesicoureteric reflux [4, 5].…”

“…We have previously characterized the morphology, Ca signals, and contractility patterns in animal [33] and human [3] ureter tissues and have validated the rat as a good experimental model for the human ureter and for the study of UPEC infection [3, 34]. In addition, we have shown that 2 strains of UPEC isolated from human pyelonephritis patients (J96 and 536) have an inhibitory effect on ureteric function in both species, which is thought to be mediated by type 1 fimbriae [34].…”