John Curtin School of Medical Research, GPO Box 334, Australian National University, Canberra, ACT, 2601, Australia.
J Physiol. 2011 May 15;589(Pt 10):2607-23. doi: 10.1113/jphysiol.2010.202580. Epub 2011 Mar 21.
Blood flow is adjusted to tissue demand through rapidly ascending vasodilatations resulting from conduction of hyperpolarisation through vascular gap junctions. We investigated how these dilatations can spread without attenuation if mediated by an electrical signal. Cremaster muscle arterioles were studied in vivo by simultaneously measuring membrane potential and vessel diameter. Focal application of acetylcholine elicited hyperpolarisations which decayed passively with distance from the local site,while dilatation spread upstream without attenuation. Analysis of simultaneous recordings at the local site revealed that hyperpolarisation and dilatation were only linearly related over a restricted voltage range to a threshold potential, beyond which dilatation was maximal. Experimental data could be simulated in a computational model with electrotonic decay of hyperpolarisation but imposition of this threshold. The model was tested by reducing the amplitude of the local hyperpolarisation which led to entry into the linear range closer to the local site and decay of dilatation. Serial section electron microscopy and light dye treatment confirmed that the spread of dilatation occurred through the endothelium and that the two cell layers were tightly coupled. Generality of the mechanism was demonstrated by applying the model to the attenuated propagation of dilatation found in larger arteries.We conclude that long distance spread of locally initiated dilatations is not due to a regenerative electrical phenomenon, but rather a restricted linear relationship between voltage and vessel tone, which minimises the impact of electrotonic decay of voltage. Disease-related alterations in endothelial coupling or ion channel expression could therefore decrease the ability to adjust blood flow to meet metabolic demand.
血流通过通过血管缝隙连接进行超极化传导而迅速上升的血管舒张来适应组织需求。我们研究了如果这些舒张是由电信号介导的，它们如何在没有衰减的情况下传播。通过同时测量膜电位和血管直径，在体研究了提睾肌小动脉。局部应用乙酰胆碱可引发超极化，超极化随距离局部部位的增加而被动衰减，而舒张则无衰减地向上游传播。在局部部位同时记录的分析表明，超极化和舒张仅在有限的电压范围内与阈值电位呈线性相关，超过该阈值，舒张达到最大值。在一个具有超极化电衰减的计算模型中，可以模拟实验数据，但要施加该阈值。通过降低局部超极化的幅度来测试模型，这导致进入线性范围更接近局部部位，并导致舒张衰减。连续切片电子显微镜和光染料处理证实，舒张的传播是通过内皮细胞进行的，并且这两个细胞层紧密偶联。该模型应用于较大动脉中发现的舒张衰减传播，证明了该机制的普遍性。我们得出结论，局部起始舒张的远距离传播不是由于再生电现象，而是电压和血管张力之间的受限线性关系，这最大限度地减少了电压电衰减的影响。因此，内皮偶联或离子通道表达的疾病相关改变可能会降低调节血流以满足代谢需求的能力。
