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A "dual action" control system that enables sodium channels to play a vital role in maintaining normal blood pressure has been discovered by Prof. Haim Garty, Dr. Carol Asher and co-workers at the Institute's Department of Membrane Research and Biophysics. Since abnormalities in this mechanism are a major cause of hypertension, the research may lead to more effective drugs for this disorder.
Salt -- in the form of sodium and chloride ions -- is transported into the blood through special channels located in the inner linings of the kidney, colon and urinary bladder. If too much salt enters the circulatory system, water follows in its wake, resulting in high blood pressure. Thus the body possesses a sophisticated mechanism for regulating the flow of sodium ion -- a task performed mainly by the steroid hormone aldosterone. Prof. Garty's group has now discovered a "dual action" process underlying aldosterone-sodium channel interaction.
The researchers injected frog oocytes, the germ cells contained in ovaries, with RNA isolated from toad tissue incubated in the presence of aldosterone. Short incubation periods doubled the channel activity without producing new channel RNA, whereas long incubation periods not only stepped up the activity in the existing channels but also triggered the manufacture of new ones. In a corroboratory study with Prof. Nathan Dascal of the Sackler School of Medicine at Tel Aviv University, RNA extracted from intestinal tissues of chickens that were fed a low-salt diet readily produced channels in frog oocytes, while no channel activity was detected in oocytes injected with RNA isolated from chickens given a high-salt diet. Both studies indicate that the enhancement of channel performance is controlled by a mechanism different from the one that induces the manufacture of new channels.
Certain anti-hypertensive drugs, such as diuretic amiloride, combat high blood pressure by blocking sodium transport through the channels. However, these drugs are not highly specific and produce side effects. Prof. Garty is now attempting to clone the sodium channel and identify its amiloride binding site -- key steps in the design of more potent and specific drugs to combat high blood pressure.
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