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 (BK(C) (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 BK(C) (a) channel properties in patients at different ages to assess the effects of hypertension and aging on the functional changes of BK(C) (a) channels. METHODS AND RESULTS: Patch clamp was performed to detect the activities of BK(C) (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 BK(C) (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 BK(C) (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 BK(C) (a) channels in human mesenteric artery smooth muscle cells, and aging itself may also be a factor in these changes in the cells.