UTP activates small conductance Ca2+-activated K+ (SK) channels in murine detrusor PDGFRα+ cells.

UTP activates small conductance Ca2+-activated K+ (SK) channels in murine detrusor PDGFRα+ cells. Am J Physiol Renal Physiol. 2015 Jul 22;:ajprenal.00156.2015 Authors: Lee H, Koh BH, Yamasaki E, George NE, Sanders KM, Koh SD 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 PDGFRα(+) 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-/- /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 non-selective cation currents in smooth muscle cells. Under current-clamp (I=0), UTP induced significant hyperpolarization of PDGFRα(+) cells. MRS2500, a P2Y1 antagonist, did not affect the UTP-activated outward currents in PDGFRα(+) cells from wild type, and activation of outward currents by UTP was retained in P2ry1-/-/eGFP mice. As a nega...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research