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. //
