Expression and function of BK and Kv1.5 channels in aortic smooth muscle from lean and obese Zucker rats (1077.5)

We tested the hypothesis that metabolic syndrome is associated with reduced expression and function of K + channels in smooth muscle. Aortic smooth muscle from male lean and obese Zucker rats was used as a model. Whole‐cell patch clamp experiments indicated that Ca 2+ ‐activated (BK) and voltage‐dependent (K V ) K + currents dominated membrane conductance. Penitrem A (1 uM) and DPO‐1 (10 uM), selective antagonists of BK and K V 1.5 channels were used to determine the expression of these channels. In lean rats, penitrem A inhibited 37 ± 6% of current at +100 mV, whereas subsequent addition of DPO‐1 inhibited 74 ± 4% of the remaining current. In obese rats, penitrem A inhibited 19 ± 6% of current at +100 mV, whereas subsequent addition of DPO‐1 inhibited 78 ± 3% of the remaining current. The penitrem A‐sensitive BK current was 2.7 ± 0.7 fold greater in lean rats. In contrast, and surprisingly, the DPO‐1‐sensitive K V 1.5 current was 1.5 ± 0.2 fold greater in obese rats. Western blots supported the patch clamp studies, as BK channel protein was 1.4 ± 0.1 fold greater in lean rats, while K V 1.5 protein was 2.5 ± 0.4 fold greater in obese rats. These data indicate that metabolic syndrome decreases the expression of BK channels, but simultaneously increases K V 1.5 channel expression. We suggest this opposite change in K + channel expression may represent a compensatory stage of metabolic disease that serves to preserve cardiovascular function. Grant Funding Source : Supported by T32HL090610