title: UTP activates small-conductance Ca2+-activated K+ channels in murine detrusor PDGFRα+ cells.
abstract: Purines induce transient contraction and prolonged relaxation of detrusor muscles. Transient contraction is likely due to activation of inward currents in smooth muscle cells, and prolonged relaxation may be due to activation of small-conductance Ca(2+)-activated K(+) (SK) channels via P2Y1 receptors expressed by detrusor PDGF receptor (PDGFR)α(+) cells. We investigated whether other subtypes of P2Y receptors are involved in the activation of SK channels in PDGFRα(+) cells of detrusor muscles. Quantitative analysis of transcripts revealed that P2ry2, P2ry4, and P2ry14 are expressed in PDGFRα(+) cells of P2ry1-deficient/enhanced green fluorescent protein (P2ry1(-/-)/eGFP) mice at similar levels as in wild-type mice. UTP, a P2Y2/P2Y4 agonist, activated large outward currents in detrusor PDGFRα(+) cells. SK channel blockers and an inhibitor of phospholipase C completely abolished currents activated by UTP. In contrast, UTP activated nonselective cation currents in smooth muscle cells. Under current-clamp (current = 0), UTP induced significant hyperpolarization of PDGFRα(+) cells. MRS2500, a selective P2Y1 antagonist, did not affect UTP-activated outward currents in PDGFRα(+) cells from wild-type mice, and activation of outward currents by UTP was retained in P2ry1(-/-)/eGFP mice. As a negative control, we tested the effect of MRS2693, a selective P2Y6 agonist. This compound did not activate outward currents in PDGFRα(+) cells, and currents activated by UTP were unaffected by MRS2578, a selective P2Y6 antagonist. The nonselective P2Y receptor blocker suramin inhibited UTP-activated outward currents in PDGFRα(+) cells. Our data demonstrate that P2Y2 and/or P2Y4 receptors function, in addition to P2Y1 receptors, in activating SK currents in PDGFRα(+) cells and possibly in mediating purinergic relaxation responses in detrusor muscles.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada.
authors.forename: Haeyeong
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada.
authors.forename: Byoung H
authors.initials: BH
authors.lastname: Koh
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada.
authors.forename: Evan
authors.initials: E
authors.lastname: Yamasaki
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada.
authors.forename: Nikita E
authors.initials: NE
authors.lastname: George
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada.
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada skoh@medicine.nevada.edu.
authors.forename: Sang Don
authors.initials: SD
authors.lastname: Koh
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018408:Patch-Clamp Techniques; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000819:agonists*; D014544:Uridine Triphosphate / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
chemical_list: C546383:P2ry1 protein, mouse; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D051640:Small-Conductance Calcium-Activated Potassium Channels; C104749:purinoceptor P2Y4; D000255:Adenosine Triphosphate; D020796:Receptor, Platelet-Derived Growth Factor alpha; D014544:Uridine Triphosphate
keywords: detrusor relaxation; interstitial cells; potassium channels; purinergic receptors