Smooth muscle cells (SMCs) in arterioles from striated muscle display IP
3
receptor-dependent Ca
2+
waves that contribute to global myoplasmic Ca
2+
concentration and myogenic tone. However, the contribution of voltage-gated Ca
2+
channels (VGCC) to these arteriolar Ca
2+
signals is unknown. We tested the hypothesis that Ca
2+
waves depend on Ca
2+
influx through VGCC in cremaster muscle arterioles loaded with Fluo-4 and imaged by confocal microscopy. At rest, with vessels pressurized to 80 cm H
2
O in 2 mM Ca
2+
, arteriolar diameter was 28 ± 2 μm (n = 5), and SMCs displayed Ca
2+
waves with frequency (FREQ) = 0.21 ± 0.06 Hz, occurrence (OCC) = 3.5 ± 1.0 waves/SMC and amplitude (AMP) = 1.7 ± 0.1 F/Fo. Removal of extracellular Ca
2+
dilated the arterioles to 39 ± 1 μm, and inhibited Ca
2+
waves (FREQ = 0.1 ± 0.03, OCC = 1.7 ± 0.5 waves/SMC and AMP = 1.4 ± 0.06 F/Fo; p < 0.05 vs. rest) indicating that Ca
2+
waves depended, in part, on influx of extracellular Ca
2+
. Similarly, the VGCC antagonist, nifedipine (1 μM), dilated the arterioles to 34 ± 1.3 μm and also inhibited Ca
2+
waves (FREQ = 0.07 ± 0.02 Hz, OCC = 1.1 ± 0.5 waves/SMC, AMP = 1.4 ± 0.05 F/Fo; p < 0.05 vs. rest). Hyperpolarization of SMCs with the K
+
channel agonist, cromakalim (10 μM), dilated arterioles from 49 ± 3 to 59 ± 4 μm (n = 4, p < 0.05) and also reduced Ca
2+
wave FREQ (0.1 ± 0.04 to 0.03 ± 0.003 Hz), OCC (1.7 ± 0.04 to 0.5 ± 0.05 waves/SMC) and AMP (1.5 ± 0.04 to 1.2 ± 0.004 F/Fo) (p < 0.05). Conversely, depolarization of SMCs with the BK
Ca
channel blocker, TEA (1 mM), constricted arterioles from 28 ± 2 to 16 ± 1 μm (n = 5, p < 0.05) and increased wave FREQ (0.2 ± 0.1 to 0.5 ± 0.1 Hz, p < 0.05) and OCC (4 ± 1 to 8 ± 2 waves/SMC, p < 0.05), effects blocked by nifedipine (1μM) (p < 0.05). Similarly, in arterioles pressurized to 20 cm H
2
O to eliminate myogenic tone and reduce basal VGCC activity, application of the VGCC agonist, BayK 8644 (5 nM) constricted the arterioles from 14 ± 1 to 8 ± 1 μm and increased wave FREQ (0.2 ± 0.1 to 0.6 ± 0.1 Hz) and OCC (3 ± 1 to 10 ± 1 waves/SMC) (n = 6; p < 0.05), effects that were independent of ryanodine receptors, as Ca
2+
waves were unaffected by ryanodine (50 μM) in the absence or presence of BayK 8644 (n = 6; p > 0.05). These data support the hypothesis that Ca
2+
waves in arteriolar SMCs depend, in part, on Ca
2+
influx through VGCC.
Regulation of fetoplacental vascular bed by hypoxia
