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

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