Role of Ca²⁺ entry and Ca²⁺ stores in atypical smooth muscle cell autorhythmicity in the mouse renal pelvis

Background and purpose:

Electrically active atypical smooth muscle cells (ASMCs) within the renal pelvis have long been considered to act as pacemaker cells driving pelviureteric peristalsis. We have investigated the role of Ca²⁺ entry and uptake into and release from internal stores in the generation of Ca²⁺ transients and spontaneous transient depolarizations (STDs) in ASMCs.

Experimental approach:

The electrical activity and separately visualized changes in intracellular Ca²⁺ concentration in typical smooth muscle cells (TSMCs), ASMCs and interstitial cells of Cajal‐like cells (ICC‐LCs) were recorded using intracellular microelectrodes and a fluorescent Ca²⁺ indicator, fluo‐4.

Results:

In 1 μM nifedipine, high frequency (10–30 min⁻¹) Ca²⁺ transients and STDs were recorded in ASMCs, while ICC‐LCs displayed low frequency (1–3 min⁻¹) Ca²⁺ transients. All spontaneous electrical activity and Ca²⁺ transients were blocked upon removal of Ca²⁺ from the bathing solution, blockade of Ca²⁺ store uptake with cyclopiazonic acid (CPA) and with 2‐aminoethoxy‐diphenylborate (2‐APB). STD amplitudes were reduced upon removal of the extracellular Na⁺ or blockade of IP₃ dependent Ca²⁺ store release with neomycin or U73122. Blockade of ryanodine‐sensitive Ca²⁺ release blocked ICC‐LC Ca²⁺ transients but only reduced Ca²⁺ transient discharge in ASMCs. STDs in ASMCS were also little affected by DIDS, La³⁺, Gd³⁺ or by the replacement of extracellular Cl^‐ with isethionate.

Conclusions:

ASMCs generated Ca²⁺ transients and cation‐selective STDs via mechanisms involving Ca²⁺ release from IP₃‐dependent Ca²⁺ stores, STD stimulation of TSMCs was supported by Ca²⁺ entry through L type Ca²⁺ channels and Ca²⁺ release from ryanodine‐sensitive stores.

DOI: 10.1038/sj.bjp.0707535

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