SUR2 subtype (A and B)‐dependent differential activation of the cloned ATP‐sensitive K + channels by pinacidil and nicorandil

The classical ATP sensitive K + (K ATP ) channels are composed of a sulphonylurea receptor (SUR) and an inward rectifying K + channel subunit (BIR/Kir6.2). They are the targets of vasorelaxant agents called K + channel openers, such as pinacidil and nicorandil. In order to examine the tissue selectivity of pinacidil and nicorandil, in vitro , we compared the effects of these agents on cardiac type (SUR2A/Kir6.2) and vascular smooth muscle type (SUR2B/Kir6.2) of the K ATP channels heterologously expressed in HEK293T cells, a human embryonic kidney cell line, by using the patch‐clamp method. In the cell‐attached recordings (145 m M K + in the pipette), pinacidil and nicorandil activated a weakly inwardly‐rectifying, glibenclamide‐sensitive 80 pS K + channel in both the transfected cells. In the whole‐cell configuration, pinacidil showed a similar potency in activating the SUR 2B /Kir6.2 and SUR 2A /Kir6.2 channels (EC 50 of ∼2 and ∼10 μ M , respectively). On the other hand, nicorandil activated the SUR 2B /Kir6.2 channel >100 times more potently than the SUR 2A /Kir6.2 (EC 50 of ∼10 μ M and >500 μ M , respectively). Thus, nicorandil, but not pinacidil, preferentially activates the K ATP channels containing SUR 2B . Because SUR 2A and SUR 2B are diverse only in 42 amino acids at their C‐terminal ends, it is strongly suggested that this short part of SUR 2B may play a critical role in the action of nicorandil on the vascular type classical K ATP channel.