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

William F. Jackson, Erika M. Boerman
2018 American Journal of Physiology. Heart and Circulatory Physiology  
Jackson WF, Boerman EM. Voltage-gated Ca 2ϩ 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 Ca 2ϩ waves that contribute to global myoplasmic Ca 2ϩ concentration and myogenic tone. However, the contribution made by voltage-gated Ca 2ϩ channels (VGCCs) to arteriolar SMC Ca 2ϩ waves is unknown. We tested the hypothesis that VGCC activity
more » ... GCC activity modulates SMC Ca 2ϩ waves in pressurized (80 cmH2O/59 mmHg, 34°C) hamster cremaster muscle arterioles loaded with Fluo-4 and imaged by confocal microscopy. Removal of extracellular Ca 2ϩ dilated arterioles (32 Ϯ 3 to 45 Ϯ 3 m, n ϭ 15, P Ͻ 0.05) and inhibited the occurrence, amplitude, and frequency of Ca 2ϩ waves (n ϭ 15, P Ͻ 0.05), indicating dependence of Ca 2ϩ waves on Ca 2ϩ influx. Blockade of VGCCs with nifedipine (1 M) or diltiazem (10 M) or deactivation of VGCCs by hyperpolarization of smooth muscle with the K ϩ channel agonist cromakalim (10 M) produced similar inhibition of Ca 2ϩ waves (P Ͻ 0.05). Conversely, depolarization of SMCs with the K ϩ channel blocker tetraethylammonium (1 mM) constricted arterioles from 26 Ϯ 3 to 14 Ϯ 2 m (n ϭ 11, P Ͻ 0.05) and increased wave occurrence (9 Ϯ 3 to 16 Ϯ 3 waves/SMC), amplitude (1.6 Ϯ 0.07 to 1.9 Ϯ 0.1), and frequency (0.5 Ϯ 0.1 to 0.9 Ϯ 0.2 Hz, n ϭ 10, P Ͻ 0.05), effects that were blocked by nifedipine (1 M, P Ͻ 0.05). Similarly, the VGCC agonist Bay K8644 (5 nM) constricted arterioles from 14 Ϯ 1 to 8 Ϯ 1 m and increased wave occurrence (3 Ϯ 1 to 10 Ϯ 1 waves/SMC) and frequency (0.2 Ϯ 0.1 to 0.6 Ϯ 0.1 Hz, n ϭ 6, P Ͻ 0.05), effects that were unaltered by ryanodine (50 M, n ϭ 6, P Ͼ 0.05). These data support the hypothesis that Ca 2ϩ 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 Ca 2ϩ influx through voltage-gated Ca 2ϩ channels and release of Ca 2ϩ from internal stores through inositol 1,4,5-trisphosphate receptors in the form of Ca 2ϩ waves to maintain pressure-induced smooth muscle tone.
doi:10.1152/ajpheart.00292.2018 pmid:29957015 fatcat:mxmyuuqqq5advb2nkgdchtjjze