| First Author | Lee H | Year | 2015 |
| Journal | Am J Physiol Renal Physiol | Volume | 309 |
| Issue | 6 | Pages | F569-74 |
| PubMed ID | 26202222 | Mgi Jnum | J:284481 |
| Mgi Id | MGI:6382351 | Doi | 10.1152/ajprenal.00156.2015 |
| Citation | Lee H, et al. (2015) UTP activates small-conductance Ca2+-activated K+ channels in murine detrusor PDGFRalpha+ cells. Am J Physiol Renal Physiol 309(6):F569-74 |
| abstractText | 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)alpha(+) cells. We investigated whether other subtypes of P2Y receptors are involved in the activation of SK channels in PDGFRalpha(+) cells of detrusor muscles. Quantitative analysis of transcripts revealed that P2ry2, P2ry4, and P2ry14 are expressed in PDGFRalpha(+) 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 PDGFRalpha(+) 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 PDGFRalpha(+) cells. MRS2500, a selective P2Y1 antagonist, did not affect UTP-activated outward currents in PDGFRalpha(+) 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 PDGFRalpha(+) 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 PDGFRalpha(+) cells. Our data demonstrate that P2Y2 and/or P2Y4 receptors function, in addition to P2Y1 receptors, in activating SK currents in PDGFRalpha(+) cells and possibly in mediating purinergic relaxation responses in detrusor muscles. |
