IP 3 receptors, but not ryanodine receptors mediate subsarcolemmal Ca 2+ oscillations in arteriolar smooth muscle cells

The role of ryanodine receptors (RYR) and IP 3 receptors (IP 3 R) in Ca 2+ signalling in arteriolar smooth muscle cells (ASMC) has not been established. Therefore, we tested the hypothesis that RYR and IP 3 R mediate subsarcolemmal Ca 2+ oscillations (OSC) in ASMC. Second or 3 rd order hamster cremaster arterioles were cannulated, loaded with 5 μM Fluo‐4 AM for confocal measurement of OSC and pressurized to 80 cm H 2 O at 34 °C. In 6 vessels with myogenic tone, OSC were observed in 47 ± 9% of ASMC along vessels, with amplitude (AMP) = 1.42 ± 0.09 (Fluo‐4 intensity relative to baseline, F/F o ) and frequency (FRE) = 0.33 ± 0.06 s −1 . The RYR antagonist, ryanodine (RYD; 10 μM) had no effect on OSC. With RYD, OSC were observed in 48 ± 9% of ASMC with AMP = 1.46 ± 0.10 F/F o and FRE = 0.34 ± 0.06 s −1 (n = 6, p > 0.05), although 10 μM RYD abolished Ca 2+ signals induced by the RYR agonist, caffeine (10 mM; p < 0.05), demonstrating the efficacy of RYD. In contrast, the IP 3 R antagonist, 2‐aminoethoxydiphenyl borate (2‐APB;100 μM) significantly decreased OSC occurrence (from 48 ± 5% to 11 ± 6%), AMP (from 1.67 ± 0.06 to 1.04 ± 0.05 F/F o ), and FRE (from 0.21 ± 0.06 to 0.04 ± 0.01 s −1 ) (n = 6, p < 0.05). Similarly, OSC were inhibited by xestospongin D (5 μM; n = 3, p < 0.05), another IP 3 R antagonist. Thus, IP 3 R, but not RYR, mediate subsarcolemmal Ca 2+ oscillations in arteriolar smooth muscle cells. Supported by PHS grants HL 32469 & HL 086483 to WFJ and AHA Fellowship 0815778G to EMB.