Contribution of kv7 channels to acetylcholine‐induced dilation in human adipose arterioles

Abstract

Voltage‐gated K+ (KV) channels, especially shaker‐related KV1, serve as important regulators of vascular tone and reactivity. Emerging evidence suggests that KCNQ or KV7 channels may represent another subfamily of KV channels contributing to vascular tone regulation. Functional KV7 channels have been detected in vascular smooth muscle and endothelial cells of several vascular beds, although their significance in mediating physiological responses remains largely unclear. We investigated the contribution of KV7 channels to acetylcholine (ACh)‐induced dilation in ex vivo human adipose arterioles. Fresh adipose tissues were obtained as discarded surgical specimens from subjects without and with coronary artery disease (non‐CAD and CAD, respectively), and arterioles (100–200 μm, internal diameter) were dissected and cannulated under 60 mmHg and examined for diameter changes using video microscopy. In arterioles from non‐CAD subjects, ACh (10−9–10−5 M) induced potent vasodilation in a concentration‐dependent manner (% maximal dilation at 10−7 and 10−5 M, 62±6 and 93±2, respectively, n=6). KV7 channel blocker linopirdine (10 μM) significantly reduced the dilation to 10−7 M ACh (% dilation 18±6 vs. 62±6 in control), whereas blockade of KV1.5 (a major KV1 channel in human adipose arterioles) by DPO‐1 (1 μM) or Psora‐4 (30 nM) was without effect. In arterioles pretreated with L‐NAME (100 μM, a nitric oxide synthase inhibitor) and indomethacin (10 μM, a prostacyclin inhibitor), linopirdine also reduced ACh‐induced dilation (% dilation to 10−7 ACh, 10±4 vs. 30±6 in control with L‐NAME and indomethacin, and % dilation to 10−6 M ACh, 45±8 vs. 80±4 in control with L‐NAME and indomethacin). In contrast to arterioles from non‐CAD subjects, ACh‐elicited dilation in CAD arterioles was not affected by linopirdine (% dilation at 10−7 M, 57±4 vs. 66±7 in control). These results indicate that KV7 channels are involved in ACh‐induced dilation in human adipose arterioles from non‐CAD subjects and part of this effect is related to an endothelium‐dependent hyperpolarization (EDH) mechanism of dilation. In addition, the involvement of KV7 in ACh‐induced arteriolar dilation seems to be reduced in subjects with disease (CAD). This study provides further support for the recruitment of KV7 to the functional K+ channel repertoire in vascular cells.Support or Funding InformationNational Heart, Lung and Blood Institute Grant R01‐HL 096647