Different Effects of Hypertension and Age on the Function of Large Conductance Calcium- and Voltage-Activated Potassium Channels in Human Mesentery Artery Smooth Muscle Cells.

BACKGROUND:Large-conductance calcium- and voltage-activated potassium channels (BKC a channels) play important roles in the maintenance of vascular tone, and their dysregulation is associated with abnormal vascular relaxation and contraction. We tested the changes in BKC a channel properties in patients at different ages to assess the effects of hypertension and aging on the functional changes of BKC a channels. METHODS AND RESULTS:Patch clamp was performed to detect the activities of BKC a channels in freshly isolated human mesenteric artery smooth muscle cells from younger patients (aged ≤45 years) without hypertension, older patients (aged ≥65 years) without hypertension, and older patients with hypertension. The expression of mRNA and protein from BKC a channels was evaluated by reverse transcription polymerase chain reaction and Western blot analysis, respectively. Results showed that the whole-cell current density, spontaneous transient outward current, and Ca(2+) sensitivity of the artery smooth muscle cells were significantly decreased in the older patients with hypertension; the decreases were insignificant in the older patients without hypertension, although a clear tendency to have spontaneous transient outward current was detected in these patients. The expression of both mRNA and protein of BKC a subunits α and β1 was significantly decreased in the older patients with hypertension but not in the older patients without hypertension compared with the younger patients without hypertension. CONCLUSIONS:Our findings demonstrate for the first time that hypertension is an important factor for the pathological alteration of the properties of BKC a channels in human mesenteric artery smooth muscle cells, and aging itself may also be a factor in these changes in the cells.