CWRU scientists reveal how magnesium works on ion channels important for regulating blood pressure

Researchers at Case Western Reserve University report in the August 22 issue of Nature how magnesium activates microscopic ion channels in the membrane of a cell. These particular ion channels are important in controlling blood pressure. Scientists, the researchers say, can use this new finding in the quest to understand how magnesium helps to decrease blood pressure and also treat heart failure and stroke.

Calcium activated potassium channels are important microscopic pathways in the cell membrane that relax the smooth muscle in a blood vessel, according to the researchers. They also modify electrical impulses, which travel in nerve cells throughout the brain.

“Research of this kind may help to understand why some therapies such as magnesium supplements are important in the prevention and management of hypertension or heart failure,” said Jianmin Cui, the lead researcher and assistant professor in the department of biomedical engineering at CWRU. “Along with some other groups, we have discovered that when magnesium is applied to calcium-activated potassium channels, these channels will open. We know from literature that the opening of these channels can reduce blood pressure.”

The Nature article (“Mechanism of magnesium activation of calcium activated potassium channels”) was written by Jianmin Cui, the principal researcher, who was assisted by Jingyi Shi, senior researcher in the department of biomedical engineering; Gayathri Krishnamoorty and Lei Hu, graduate students in the department of biomedical engineering; and Neha Chaturvedi and Dina Harilal, undergraduates students. The team is collaborating with Yanwu Yang and Jun Qin, structural biologists at the Cleveland Clinic Foundation. The research is supported by a $1 million grant from the National Institutes of Health, Heart Lung and Blood Institute.

“The completion of stage one of the project is due to the combination of state-of-the-art bioelectric facilities and advanced structural biology results,” Cui said. “The collaboration between the department of biomedical engineering and The Cleveland Clinic Foundation was key.”

CWRU researchers used cloned ion channel DNA to express the ion channels in frog eggs. The ion channels are proteins made of various amino acids; the researchers mutated some of these amino acids and recorded functional change that resulted from the mutations.

Hypertension, Cui explained, results from the contraction of blood vessels, which causes an increase in blood pressure. “The diameter of blood vessels is controlled by smooth muscle cells around them,” he said. “When magnesium reaches these potassium channels, the channels open causing blood vessels to dilate and therefore reduce hypertension.”

According to the National Health and Nutrition Examination Survey conducted between 1988 and 1994 by The National High Blood Pressure Education Program, an estimated 42.3 million people in the U.S had hypertension. Doctors had told an additional 7.7 million on two or more occasions that they had hypertension, which gives a total of 50 million hypertensives.

“Our research is basic science, however, we hope that the results can help to explain why some treatments would work and provide rationale for development of new drugs for hypertension,” Cui said.

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