Voltage-gated Ca2+ channel activity modulates smooth muscle cell calcium waves in hamster cremaster arterioles

Cremaster muscle arteriolar smooth muscle cells (SMCs) display inositol 1,4,5-trisphosphate receptor-dependent Ca2+ waves that contribute to global myoplasmic Ca2+ concentration and myogenic tone. However, the contribution made by voltage-gated Ca2+ channels (VGCCs) to arteriolar SMC Ca2+ waves is unknown. We tested the hypothesis that VGCC activity modulates SMC Ca2+ waves in pressurized (80 cmH(2)O/59 mmHg, 34 degrees C) hamster cremaster muscle arterioles loaded with Fluo-4 and imaged by confocal microscopy. Removal of extracellular Ca2+ dilated arterioles (32 +/- 3 to 45 +/- 3 mu m, n = 15, P < 0.05) and inhibited the occurrence, amplitude, and frequency of Ca2+ waves (n = 15, P < 0.05), indicating dependence of Ca2+ waves on Ca2+ influx. Blockade of VGCCs with nifedipine (1 mu M) or diltiazem (10 mu M) or deactivation of VGCCs by hyperpolarization of smooth muscle with the K+ channel agonist cromakalim (10 mu M) produced similar inhibition of Ca2+ waves (P < 0.05). Conversely, depolarization of SMCs with the K+ channel blocker tetraethylammonium (1 mM) constricted arterioles from 26 +/- 3 to 14 +/- 2 mu m (n = 11, P < 0.05) and increased wave occurrence (9 +/- 3 to 16 +/- 3 waves/SMC), amplitude (1.6 +/- 0.07 to 1.9 +/- 0.1), and frequency (0.5 +/- 0.1 to 0.9 +/- 0.2 Hz, n = 10, P < 0.05), effects that were blocked by nifedipine (1 mu M, P < 0.05). Similarly, the VGCC agonist Bay K8644 (5 nM) constricted arterioles from 14 +/- 1 to 8 +/- 1 mu m and increased wave occurrence (3 +/- 1 to 10 +/- 1 waves/SMC) and frequency (0.2 +/- 0.1 to 0.6 +/- 0.1 Hz, n = 6, P < 0.05), effects that were unaltered by ryanodine (50 mu M, n = 6, P > 0.05). These data support the hypothesis that Ca2+ waves in arteriolar SMCs depend, in part, on the activity of VGCCs. NEW & NOTEWORTHY Arterioles that control blood flow to and within skeletal muscle depend on Ca2+ influx through voltage-gated Ca2+ channels and release of Ca2+ from internal stores through inositol 1,4,5-trisphosphate receptors in the form of Ca2+ waves to maintain pressure-induced smooth muscle tone.