Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-Ku, Nagoya, 467-8601, Japan.
Pflugers Arch. 2017 Sep;469(9):1189-1202. doi: 10.1007/s00424-017-1978-y. Epub 2017 Apr 21.
Synchrony of spontaneous Ca transients among venular mural cells (smooth muscle cells and pericytes) in visceral organs relies on the intercellular spread of L-type voltage-dependent Ca channel (LVDCC)-dependent depolarisations. However, the mechanisms underlying the synchrony of spontaneous Ca transients between arteriolar mural cells are less understood. The spontaneous intracellular Ca dynamics of arteriolar mural cells in the rat rectal submucosa were visualised by Cal-520 Ca imaging to analyse their synchrony. The mural cells in fine arterioles that had a rounded cell body with several extended processes developed spontaneous 'synchronous' Ca transients arising from Ca released from sarcoendoplasmic reticulum Ca stores. Gap junction blockers (3 μM carbenoxolone, 10 μM 18β-glycyrrhetinic acid), a Ca-activated Cl channel (CaCC) blocker (100 μM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) or lowering extracellular Cl concentration (from 134.4 to 12.4 mM) disrupted the synchrony of Ca transients between arteriolar mural cells. Blockers of T-type voltage-dependent Ca channels (TVDCCs, 1 μM mibefradil or ML218) or LVDCCs (1 μM nifedipine) reduced the Ca transient frequency or their area under curve (AUC), respectively. However, neither TVDCC nor LVDCC blockers disrupted the synchrony of Ca transients among arteriolar mural cells. This is in contrast with rectal venules in which nifedipine disrupted the synchrony of spontaneous Ca transients. Thus, spontaneous transient depolarisations arising from the opening of CaCCs may effectively spread to neighbouring arteriolar mural cells via gap junctions to maintain the Ca transient synchrony. Activation of TVDCCs appears to accelerate spontaneous Ca transients, while LVDCCs predominantly contribute to the duration of Ca transients.
内脏器官静脉壁细胞（平滑肌细胞和周细胞）自发性钙瞬变的同步性依赖于细胞间 L 型电压依赖性钙通道（LVDCC）依赖性去极化的传播。然而，血管平滑肌细胞自发性钙瞬变同步性的机制尚不清楚。通过 Cal-520 Ca 成像观察大鼠直肠黏膜下细动脉壁细胞的自发性细胞内 Ca 动力学，分析其同步性。具有圆形胞体和几个延伸突起的细动脉壁细胞中，肌源性 Ca 释放引起的自发性“同步”钙瞬变。缝隙连接阻滞剂（3 μM 氨甲环酸、10 μM 18β-甘草次酸）、钙激活氯离子通道（CaCC）阻滞剂（100 μM 4,4'-二异硫氰基二苯乙烯-2,2'-二磺酸）或降低细胞外 Cl 浓度（从 134.4 降至 12.4 mM）破坏了血管平滑肌细胞间钙瞬变的同步性。T 型电压依赖性钙通道（TVDCC）阻滞剂（1 μM 米贝地尔或 ML218）或 LVDCC 阻滞剂（1 μM 硝苯地平）分别降低钙瞬变频率或曲线下面积（AUC）。然而，TVDCC 或 LVDCC 阻滞剂均未破坏血管平滑肌细胞间钙瞬变的同步性。这与直肠小静脉形成对比，硝苯地平破坏了自发性钙瞬变的同步性。因此，CaCC 开放引起的自发性瞬时去极化可能通过缝隙连接有效传播到邻近的血管平滑肌细胞，以维持钙瞬变的同步性。TVDCC 的激活似乎加速了自发性钙瞬变，而 LVDCC 主要影响钙瞬变的持续时间。
