Distinct roles of PMCA isoforms in Ca2+homeostasis of bladder smooth muscle: evidence from PMCA gene-ablated mice
| Autor: | Richard J. Paul, Gary E. Shull, Gbolahan Okunade, Gail J. Pyne-Geithman, Yukisato Ishida, Li Liu |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Gene isoform
medicine.medical_specialty Physiology Ratón Receptors Drug Urinary Bladder chemistry.chemical_element Calcium Biology Potassium Chloride Mice Plasma Membrane Calcium-Transporting ATPases Smooth muscle Internal medicine medicine Animals Homeostasis Gene Mice Knockout Dose-Response Relationship Drug Osmolar Concentration Muscle Smooth Intracellular Membranes Cell Biology Cell biology Isoenzymes Kinetics Endocrinology chemistry Carbachol Ca2 homeostasis Muscle Contraction Signal Transduction |
| Zdroj: | American Journal of Physiology-Cell Physiology. 292:C423-C431 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00313.2006 |
| Popis: | We previously showed that plasma membrane Ca2+-ATPase (PMCA) activity accounted for 25–30% of relaxation in bladder smooth muscle ( 8 ). Among the four PMCA isoforms only PMCA1 and PMCA4 are expressed in smooth muscle. To address the role of these isoforms, we measured cytosolic Ca2+([Ca2+]i) using fura-PE3 and simultaneously measured contractility in bladder smooth muscle from wild-type (WT), Pmca1+/−, Pmca4+/−, Pmca4−/−, and Pmca1+/−Pmca4−/−mice. There were no differences in basal [Ca2+]ivalues between bladder preparations. KCl (80 mM) elicited both larger forces (150–190%) and increases in [Ca2+]i(130–180%) in smooth muscle from Pmca1+/−and Pmca1+/−Pmca4−/−bladders than those in WT or Pmca4−/−. The responses to carbachol (CCh: 10 μM) were also greater in Pmca1+/−(120–150%) than in WT bladders. In contrast, the responses in Pmca4−/−and Pmca1+/−Pmca4−/−bladders to CCh were significantly smaller (40–50%) than WT. The rise in half-times of force and [Ca2+]iincreases in response to KCl and CCh, and the concomitant half-times of their decrease upon washout of agonist were prolonged in Pmca4−/−(130–190%) and Pmca1+/−Pmca4−/−(120–250%) bladders, but not in Pmca1+/−bladders with respect to WT. Our evidence indicates distinct isoform functions with the PMCA1 isoform involved in overall Ca2+clearance, while PMCA4 is essential for the [Ca2+]iincrease and contractile response to the CCh receptor-mediated signal transduction pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|