Properties of SK3 channel-expressing PDGFRα (+) cells in the rodent urinary bladder

• Published in: European journal of pharmacology 2019-10, Vol.860, p.172552-172552, Article 172552
• Main Authors: Hayashi, Tokumasa, Hashitani, Hikaru, Takeya, Mitsue, Uemura, Kei-ichiro, Nakamura, Kei-ichiro, Igawa, Tsukasa
• Format: Article
• Language: English
• Subjects: Animals; Calcium Signaling - drug effects; Female; Gene Expression Regulation - drug effects; Guinea Pigs; Interstitial cell; Male; Mice; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; P2Y receptor; Platelet-derived growth factor receptor-α (PDGFRα); Purinergic Agonists - pharmacology; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Small-conductance calcium-activated potassium (SK3) channel; Small-Conductance Calcium-Activated Potassium Channels - metabolism; Urinary bladder; Urinary Bladder - cytology; Urinary Bladder - physiology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2019.172552

Localisation of platelet-derived growth factor receptor-α (PDGFRα) (+) cells expressing small-conductance Ca2+-activated K+ (SK3) channels in the urinary bladder was investigated, while putative roles of SK3 (+) PDGFRα (+) cells in suppressing detrusor smooth muscle (DSM) spontaneous activity were explored. In guinea-pig bladder, immunohistochemistry for SK3 channels, PDGFRα or vimentin was examined, as were the effects of purinergic agonists on spontaneous phasic contractions (SPCs). In bladder of PDGFRα-GFP mice, the effects of purinergic agonists on intracellular Ca2+ signaling in PDGFRα (+) cells or DSM cells in situ and SPCs were investigated. SK3 (+) cells co-expressing PDGFRα or vimentin were distributed in DSM bundles but not inter-bundle spaces or lamina propria. SK3 (+) cells had a stellate- or spindle-shape cell body extending processes. MRS2365 (100 nM or 1 μM), a P2Y1 agonist, caused a transient contraction without inhibiting SPCs in both DSM and lamina propria. In PDGFRα-GFP mice bladder, MRS2365, (100 nM), ADP (100 μM) or ATP (100 μM) increased the Ca2+ level of PDGFRα (+) cells without suppressing spontaneous Ca2+ transients in neighboring DSM cells, and also failed to suppress SPCs. Preferential localisation of SK3 positive PDGFRα (+) cells in DSM bundles appears to indicate their functional interaction with DSM cells. However, increases in Ca2+ level of PDGFRα (+) cells upon purinergic stimulation are not associated with the inhibition of Ca2+ or contractile activity in DSM cells. Thus, it is unlikely that the SK3-dependent hyperpolarisation generated in SK3 expressing PDGFRα (+) cells is transmitted to DSMs to suppress their excitability. [Display omitted]