Franco-Obregón A, Ureña J, López-Barneo J
Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Facultad de Medicina, Spain.
Proc Natl Acad Sci U S A. 1995 May 9;92(10):4715-9. doi: 10.1073/pnas.92.10.4715.
We have investigated the modifications of cytosolic [Ca2+] and the activity of Ca2+ channels in freshly dispersed arterial myocytes to test whether lowering O2 tension (PO2) directly influences Ca2+ homeostasis in these cells. Unclamped cells loaded with fura-2 AM exhibit oscillations of cytosolic Ca2+ whose frequency depends on extracellular Ca2+ influx. Switching from a PO2 of 150 to 20 mmHg leads to a reversible attenuation of the Ca2+ oscillations. In voltage-clamped cells, hypoxia reversibly reduces the influx of Ca2+ through voltage-dependent channels, which can account for the inhibition of the Ca2+ oscillations. Low PO2 selectively inhibits L-type Ca2+ channel activity, whereas the current mediated by T-type channels is unaltered by hypoxia. The effect of low PO2 on the L-type channels is markedly voltage dependent, being more apparent with moderate depolarizations. These findings demonstrate the existence of O2-sensitive, voltage-dependent, Ca2+ channels in vascular smooth muscle that may critically contribute to the local regulation of circulation.
我们研究了新鲜分离的动脉肌细胞中胞质[Ca2+]的变化以及Ca2+通道的活性，以测试降低氧分压（PO2）是否直接影响这些细胞中的Ca2+稳态。用fura-2 AM加载的未钳制细胞表现出胞质Ca2+的振荡，其频率取决于细胞外Ca2+内流。将PO2从150 mmHg切换到20 mmHg会导致Ca2+振荡的可逆衰减。在电压钳制的细胞中，缺氧可逆地减少通过电压依赖性通道的Ca2+内流，这可以解释Ca2+振荡的抑制。低PO2选择性抑制L型Ca2+通道活性，而T型通道介导的电流不受缺氧影响。低PO2对L型通道的影响明显依赖于电压，在中度去极化时更明显。这些发现证明了血管平滑肌中存在对氧敏感、电压依赖性的Ca2+通道，这可能对局部循环调节起关键作用。
