Regulation of Calcium Entry in Cerebral Arteries

小动脉控制着流向不同器官的血液。这些动脉通常会收缩，然后根据需要的血液进行扩张或收缩。大脑中的动脉对血液流动有特殊的要求；即使在血压变化时，它们也必须保持血液流动。钙(Ca~(2+))离子在动脉的狭窄和开放中起关键作用。动脉壁中肌肉细胞内的钙离子会导致肌肉细胞收缩，从而导致血管变窄。我们研究了钙离子进入这些肌肉细胞的机制。钙离子通过特殊的蛋白质进入平滑肌，这些蛋白质通过隔膜形成气孔，将细胞内外分开。这些毛孔被称为“钙通道”，是一类被称为“钙通道阻滞剂”的主要心血管药物的靶点，这种药物用于治疗高血压、心绞痛和中风。这项拟议的项目将研究调节大脑血液流动的动脉中的“钙通道”的特性。这应该是此类研究的第一次，并将为理解一些最重要的动脉的直径是如何调节的提供重要信息。这项研究通过新技术分离小动脉和称为WKY的遗传品系大鼠的单个平滑肌成为可能。大鼠被麻醉，并被迅速杀死。然后，动脉被迅速移除。所有的实验都是在分离的动脉或从这些动脉分离的单个平滑肌细胞上进行的。这些研究应该是此类研究中的第一个，并且应该为理解紧张性、自律性动脉中钙进入的调节提供必要的基础。//

Small arteries control blood flow to various organs. These arteries are normally contracted from which they dilate or constrict depending on the need for blood. The arteries in the brain have a special requirement for blood flow; they must maintain blood flow even when the blood pressure changes. Calcium (Ca2+) ions play a critical role in the narrowing and opening of arteries. Ca2+ ions inside the muscle cells in the wall of the arteries cause the muscle cells to contract and consequently cause blood vessels to narrow. We study the mechanism by which Ca2+ enters these muscle cells. Ca2+ enters the smooth muscle through specialized proteins that form pores through membrane that separate the outside of the cell from the inside. These pores are called "calcium channels" and are the targets of a major class of cardiovascular drugs called "calcium channel blockers" that are used to treat hypertension, angina, and stroke. The proposed project will examine the properties of "calcium channels" in arteries that regulate blood flow in the brain. This should be the first study of its kind and should provide vital information to the understanding of how the diameter of some of the most important arteries is regulated. This study has been made possible by new techniques to isolate small arteries and single smooth muscle of genetic strain of rats called WKY. The rats are anesthetized and rapidly killed. The arteries are then rapidly removed. All experiments are done on the isolated arteries or single smooth muscle cells isolated from these arteries. These studies should be the first of their kind and should provide a foundation essential for understanding the regulation of Ca entry in tonic, autoregulating arteries. //