Morphology, Calcium Signaling and Mechanical Activity in Human Ureter

Purpose

We determined the mechanisms of calcium signaling in the human ureter, and the relationship to peristaltic contractions and bundular structure in living tissue, thereby advancing the understanding of ureteral function in health and obstruction and reflux.

Materials and Methods

Confocal imaging of 31 ureters was performed and simultaneous force and calcium measurements were made. Immunohistochemistry and Western blotting were also performed.

Results

Confocal imaging showed a 3-dimensional network of smooth muscle bundles with no defined longitudinal or circular layers. Fast propagating Ca waves spread throughout the bundles, were closely associated with contraction and depended on L-type Ca channel entry. Immunohistochemistry and Western blotting demonstrated L-type Ca channels, Ca dependent K channels, sarcoplasmic reticulum Ca-adenosine triphosphatase isoforms 2 and 3, inositol triphosphate, and ryanodine receptors. Modulation of Ca and K channel activity was a potent mechanism for affecting Ca and force, whereas manipulation of the sarcoplasmic reticulum had little effect.

Conclusions

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.

Key Words: ureter, smooth muscle, sarcoplasmic reticulum, calcium channels, muscle contraction

Abbreviations and Acronyms: BK_Ca, Ca dependent K channel, CPA, cyclopiazonic acid, IP₃, inositol triphosphate, K_v, voltage dependent K channel, RyR, ryanodine receptor, SERCA, SR Ca-adenosine triphosphatase, SR, sarcoplasmic reticulum, TEA, tetraethylammonium