title: Ryanodine receptors are uncoupled from contraction in rat vena cava.
abstract: Ryanodine receptors (RyR) are Ca(2+)-sensitive ion channels in the sarcoplasmic reticulum (SR) membrane, and are important effectors of SR Ca(2+) release and smooth muscle excitation-contraction coupling. While the relationship between RyR activation and contraction is well characterized in arteries, little is known about the role of RyR in excitation-contraction coupling in veins. We hypothesized that RyR are present and directly coupled to contraction in rat aorta (RA) and vena cava (RVC). RA and RVC expressed mRNA for all 3 RyR subtypes, and immunofluorescence showed RyR protein was present in RA and RVC smooth muscle cells. RA and RVC rings contracted when Ca(2+) was re-introduced after stores depletion with thapsigargin (1μM), indicating both tissues contained intracellular Ca(2+) stores. To assess RyR function, contraction was then measured in RA and RVC exposed to the RyR activator caffeine (20mM). In RA, caffeine caused contraction that was attenuated by the RyR antagonists ryanodine (10μM) and tetracaine (100μM). However, caffeine (20mM) did not contract RVC. We next measured contraction and intracellular Ca(2+) (Ca(2+)(i)) simultaneously in RA and RVC exposed to caffeine. While caffeine increased Ca(2+)(i) and contracted RA, it had no significant effect on Ca(2+)(i) or contraction in RVC. These data suggest that ryanodine receptors, while present in both RA and RVC, are inactive and uncoupled from Ca(2+) release and contraction in RVC.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, 1355 Bogue St. Room B-445, East Lansing, MI 48824, USA. tykockin@msu.edu
authors.forename: N R
authors.initials: NR
authors.lastname: Tykocki
authors.forename: J M
authors.initials: JM
authors.lastname: Thompson
authors.forename: W F
authors.initials: WF
authors.lastname: Jackson
authors.forename: S W
authors.initials: SW
authors.lastname: Watts
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D056966:Excitation Contraction Coupling / Q000187:drug effects*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014684:Venae Cavae / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D020033:Protein Isoforms; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D002118:Calcium