Vasoregulation by a potassium channel subunit
A study showing that one subunit of an ion channel protein 'fine-tunes' vasoregulation offers a new model for the molecular basis of hypertension.
A study published in the 19 October Nature shows that one subunit of a potassium channel has a pivotal role in controlling vascular smooth muscle tone. This raises the possibility that defects in this subunit may underlie some forms of hereditary hypertension, making the channel an attractive target for new antihypertensive drugs.
A multicenter team, led by Robert Brenner from the Howard Hughes Medical Institute at Stanford University, created mice lacking the β1 subunit of the calcium-dependent potassium (BK) channel. The smooth muscle BK channels of knockout mice had reduced calcium sensitivity, and these animals developed elevated arterial tone, elevated arterial blood pressure and enlarged hearts — as seen in humans with chronic essential hypertension.
"The finding of elevated blood pressure was important because it showed us that the pressure regulatory system was as simple as we had predicted it to be," Brenner et al say. This study suggests that drugs that change β1 subunit function by altering the channel's calcium sensitivity could allow control of blood pressure with fewer side-effects than current treatments. The β1 subunit's effect in 'fine-tuning' calcium sensitivity offers a new model for researchers investigating the molecular basis of hypertension. "Since we can alter this subunit to affect blood pressure without affecting other systems, we can use it as a model to study hypertension beginning at the molecular level, through cellular physiology and to the pathology and long-term ramifications of hypertension," the team conclude.