4.6 Article

Heterogeneous function of ryanodine receptors, but not IP3 receptors, in hamster cremaster muscle feed arteries and arterioles

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00728.2010

关键词

microcirculation; ion channels; vascular smooth muscle; inositol 1,4,5-trisphosphate

资金

  1. National Heart, Lung, and Blood Institute [RO1-HL-32469, PO1-HL-070687]
  2. American Heart Association [0815778G]

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Westcott EB, Jackson WE. Heterogeneous function of ryanodine receptors, but not IP3 receptors, in hamster cremaster muscle feed arteries and arterioles. Am J Physiol Heart Circ Physiol 300: H1616-H1630, 2011. First published February 25, 2011; doi:10.1152/ajpheart.00728.2010.-The roles played by ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP(3)Rs) in vascular smooth muscle in the microcirculation remain unclear. Therefore, the function of both RyRs and IP(3)Rs in Ca2+ 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 Ca2+ sparks and Ca2+ waves, which were inhibited by the RyR antagonists ryanodine (10 mu M) or tetracaine (100 mu M). Despite the inhibition of sparks and waves, ryanodine or tetracaine increased global intracellular Ca2+ and constricted the arteries. The blockade of IP(3)Rs with xestospongin D (5 mu M) or 2-aminoethoxydiphenyl borate (100 mu M) or the inhibition of phospholipase C using U-73122 (10 mu M) also attenuated Ca2+ waves without affecting Ca2+ sparks. Importantly, the IP(3)Rs and phospholipase C antagonists decreased global intracellular Ca2+ and dilated the arteries. In contrast, cremaster arterioles displayed only Ca2+ waves: Ca2+ sparks were not observed, and neither ryanodine (10-50 mu M) nor tetracaine (100 mu M.) affected either Ca2+ 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 Ca2+ waves were attenuated by xestospongin D (5 mu M), 2-aminoethoxydiphenyl borate (100 mu M), and U-73122 (10 mu M), accompanied by decreased global intracellular Ca2+ and vasodilation. These findings highlight the contrasting roles played by RyRs and IP(3)Rs in Ca2+ signals and myogenic tone in feed arteries and demonstrate important differences in the function of RyRs between feed arteries and downstream arterioles.

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