ATP-binding cassette sub-family C member 9 (ABCC9) (SUR2)

ATP-binding cassette sub-family C member 9 (ABCC9), commonly known as Sulfonylurea receptor 2 (SUR2), is a regulatory subunit of ATP-sensitive potassium (KATP) channels [10, 13]. It exists primarily as two splice variants: SUR2A, which is predominantly expressed in cardiac and skeletal muscle, and SUR2B, which is found in vascular smooth muscle and the central nervous system [2, 4, 6]. These receptors couple the metabolic state of the cell (ATP/ADP ratio) to membrane excitability, playing a crucial role in vasodilation, cardiac stress responses, and neuroprotection [5, 8]. Mutations in the ABCC9 gene are linked to several clinical conditions, including Cantu syndrome (gain-of-function) and dilated cardiomyopathy (loss-of-function) [7, 15, 17]. Pharmacologically, SUR2 is targeted by potassium channel openers like minoxidil and nicorandil to treat hypertension and angina, as well as by sulfonylureas like glibenclamide, which can block these channels [3, 18].

Other names

Sulfonylurea receptor 2SUR2ASUR2BABCC9CANTUCMD1O

Drugs targeting SUR2A/SUR2B act as either potassium channel openers (KCOs) or blockers. KCOs bind to the SUR subunit to facilitate the opening of the associated Kir6.x pore, leading to potassium efflux and cellular hyperpolarization [3, 6, 18]. Conversely, sulfonylurea blockers bind to the receptor to inhibit channel activity, leading to membrane depolarization [4, 18].