title: Heterogeneous function of ryanodine receptors, but not IP3 receptors, in hamster cremaster muscle feed arteries and arterioles.
abstract: The roles played by ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP₃Rs) in vascular smooth muscle in the microcirculation remain unclear. Therefore, the function of both RyRs and IP₃Rs in Ca(²+) signals and myogenic tone in hamster cremaster muscle feed arteries and downstream arterioles were assessed using confocal imaging and pressure myography. Feed artery vascular smooth muscle displayed Ca(²+) sparks and Ca(²+) waves, which were inhibited by the RyR antagonists ryanodine (10 μM) or tetracaine (100 μM). Despite the inhibition of sparks and waves, ryanodine or tetracaine increased global intracellular Ca(²+) and constricted the arteries. The blockade of IP₃Rs with xestospongin D (5 μM) or 2-aminoethoxydiphenyl borate (100 μM) or the inhibition of phospholipase C using U-73122 (10 μM) also attenuated Ca(2+) waves without affecting Ca(²+) sparks. Importantly, the IP₃Rs and phospholipase C antagonists decreased global intracellular Ca(2+) and dilated the arteries. In contrast, cremaster arterioles displayed only Ca(²+) waves: Ca(²+) sparks were not observed, and neither ryanodine (10-50 μM) nor tetracaine (100 μM) affected either Ca(²+) signals or arteriolar tone despite the presence of functional RyRs as assessed by responses to the RyR agonist caffeine (10 mM). As in feed arteries, arteriolar Ca(²+) waves were attenuated by xestospongin D (5 μM), 2-aminoethoxydiphenyl borate (100 μM), and U-73122 (10 μM), accompanied by decreased global intracellular Ca(²+) and vasodilation. These findings highlight the contrasting roles played by RyRs and IP₃Rs in Ca(²+) signals and myogenic tone in feed arteries and demonstrate important differences in the function of RyRs between feed arteries and downstream arterioles.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA. ks783@msu.edu
authors.forename: Erika B
authors.initials: EB
authors.lastname: Westcott
authors.forename: William F
authors.initials: WF
authors.lastname: Jackson
mesh_terms: D000818:Animals; D001158:Arteries / Q000502:physiology*; D001160:Arterioles / Q000502:physiology*; D001896:Boron Compounds / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology; D006224:Cricetinae; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D047028:Macrocyclic Compounds / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000502:physiology*; D010080:Oxazoles / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000502:physiology*; D013748:Tetracaine / Q000494:pharmacology
chemical_list: D001896:Boron Compounds; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D010080:Oxazoles; D019837:Ryanodine Receptor Calcium Release Channel; C108642:xestospongin D; D013748:Tetracaine; D012433:Ryanodine; C109986:2-aminoethoxydiphenyl borate