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 neu rons in slices of midbrain from 9-12-d-old rats, Intracellular dialysi s with Mg2+ ATP-free solutions resulted in a membrane hyperpolarizatio n (14 +/- 6 mV), or outward current (102 +/- 27 pA) in voltage clamp, which developed over 14 +/- 1.6 min, These hyperpolarizations and outw ard currents were reversed by the K-ATP-blocking sulfonylureas tolbuta mide (100 mu M) and glibenclamide (3 mu M). This surfonylurea-sensitiv e outward current was associated with an increase in a nonrectifying ( between -50 and -130 mV) conductance of approximately 2 nS, with a rev ersal potential of -100 mV (in 2.5 mM extracellular potassium), consis tent with a potassium conductance increase, When the dialyzate contain ed Mg2+ ATP (2 mM), no slowly developing hyperpolarization or outward current occurred, and tolbutamide (200 mu M) and glibenclamide (10 mu M) did not affect membrane potential or current, Additionally, the ''p otassium channel activators'' (KCAs) lemakalim (200 mu M) and pinacidi l (50 mu M) were also without effect on the membrane potential or hold ing current in these cells, The hyperpolarizations and outward current s caused by baclofen and quinpirole, agonists at GABA(B) and D-2 recep tors, respectively, were neither blocked by sulfonylureas nor occluded by the current resulting from depletion of intracellular ATP, Thus, t hese K-ATPs appear independent of the potassium channels coupled to GA BA(B) and D-2 receptors in these cells, This ATP-regulated potassium c onductance may constitute a protective mechanism during anoxia or hypo glycemia, by restricting membrane depolarization of dopamine neurons w hen intracellular ATP levels fall.