Key result
Ryanodine receptors participate in Ca2+ sparks, Ca2+ waves, and negative feedback regulation of myogenic tone in feed arteries but are silent in downstream arterioles, whereas IP3 receptors contribute to Ca2+ waves and myogenic tone in both.
This study demonstrates that ryanodine receptors and IP₃ receptors have contrasting roles in regulating calcium signaling and myogenic tone in feed arteries, with significant functional differences in ryanodine receptors between feed arteries and downstream arterioles.
Differential ryanodine receptor roles by vessel segment are hypothesis-generating in animals; leaves open translation to human myogenic tone.
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.
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Westcott et al. (2011) studied Healthy (animal model). Ryanodine receptor and IP3 receptor antagonists vs. Control (physiological salt solution) was evaluated on Occurrence of Ca2+ sparks and waves, global intracellular Ca2+, and vessel diameter. Ryanodine receptors participate in Ca2+ sparks, Ca2+ waves, and negative feedback regulation of myogenic tone in feed arteries but are silent in downstream arterioles, whereas IP3 receptors contribute to Ca2+ waves and myogenic tone in both.
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