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

Richard John Lang, Hikaru Hashitani, Mary Anne Tonta, Hikaru Suzuki, Helena Cecilia Parkington

Research output: Contribution to journalArticleResearchpeer-review

32 Citations (Scopus)

Abstract

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 Ca(2+) entry and uptake into and release from internal stores in the generation of Ca(2+) transients and spontaneous transient depolarizations (STDs) in ASMCs.Experimental approach:The electrical activity and separately visualized changes in intracellular Ca(2+) 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 Ca(2+) indicator, fluo-4.Results:In 1 muM nifedipine, high frequency (10-30 min(-1)) Ca(2+) transients and STDs were recorded in ASMCs, while ICC-LCs displayed low frequency (1-3 min(-1)) Ca(2+) transients. All spontaneous electrical activity and Ca(2+) transients were blocked upon removal of Ca(2+) from the bathing solution, blockade of Ca(2+) 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 IP(3) dependent Ca(2+) store release with neomycin or U73122. Blockade of ryanodine-sensitive Ca(2+) release blocked ICC-LC Ca(2+) transients but only reduced Ca(2+) transient discharge in ASMCs. STDs in ASMCS were also little affected by DIDS, La(3+), Gd(3+) or by the replacement of extracellular Cl(-) with isethionate.Conclusions:ASMCs generated Ca(2+) transients and cation-selective STDs via mechanisms involving Ca(2+) release from IP(3)-dependent Ca(2+) stores, STD stimulation of TSMCs was supported by Ca(2+) entry through L type Ca(2+) channels and Ca(2+) release from ryanodine-sensitive stores.
Original languageEnglish
Pages (from-to)1248 - 1259
Number of pages12
JournalBritish Journal of Pharmacology
Volume152
Issue number8
Publication statusPublished - 2007

Cite this