Regulation of a potassium conductance in rat midbrain dopamine neurons by intracellular adenosine triphosphate (ATP) and the sulfonylureas tolbutamide and glibenclamide

摘要: The presence of adenosine triphosphate-regulated potassium channels (K-ATPs) in midbrain dopamine neurons is currently dispute. This was investigated using whole-cell patch-clamp recordings from slices 9-12-d-old rats. Intracellular dialysis with Mg2+ ATP-free solutions resulted a membrane hyperpolarization (14 +/- 6 mV), or outward current (102 27 pA) voltage clamp, which developed over 14 1.6 min. These hyperpolarizations and currents were reversed by the K-ATP-blocking sulfonylureas tolbutamide (100 microM) glibenclamide (3 microM). sulfonylurea-sensitive associated an increase nonrectifying (between -50 -130 mV) conductance approximately 2 nS, reversal potential -100 mV (in 2.5 mM extracellular potassium), consistent increase. When dialyzate contained Mg2+ATP (2 mM), no slowly developing occurred, (200 (10 did not affect current. Additionally, "potassium channel activators" (KCAs) lemakalim pinacidil (50 also without effect on holding these cells. caused baclofen quinpirole, agonists at GABAB D2 receptors, respectively, neither blocked nor occluded resulting depletion intracellular ATP. Thus, K-ATPs appear independent coupled to receptors ATP-regulated may constitute protective mechanism during anoxia hypoglycemia, restricting depolarization when ATP levels fall.