ATP-sensitive potassium channels in freshly dissociated adult rat striatal neurons: activation by metabolic inhibitors and the dopaminergic receptor agonist quinpirole.
The characteristics of adenosine 5'-triphosphate (ATP)-sensitive K+ channels in acutely isolated striatal neurons from adult rats were examined. Neurons had a resting membrane potential of -53.9+/-1.2 mV (n=66), with evoked or spontaneous action potentials firing at 10+/-0.7 Hz, and large inwards and outwards whole-cell currents. In cell-attached patches with a high [K+] in the pipette, a voltage-independent, ATP-insensitive 16.5+/-1.5 pS channel was observed in 375 out of 452 cells. Bath application of Na+-azide (0.5-2 mM) to 108 neurons revealed another 145.7+/-3.5 pS (LKATP) channel in 65 neurons; this channel was blocked by tolbutamide. The LKATP channel exhibited a high open probability (Po, 0.8+/-0.05) at 0 mV pipette potential. Varying the pipette [K+] shifted the reversal potential of LKATP, showing the channel's K+ selectivity. Cytoplasmic ATP (ATPi) reversibly inhibited LKATP, with an inhibitory constant (Ki) of 0.12 mM. LKATP was sensitive to intracellular Ca2+ but insensitive to iberiotoxin. In 25% of cell-attached patches, the presence of quinpirole in the pipette opened a third type of channel (90.6+/-1.7 pS, termed D2KATP). Sulpiride, a dopamine D2-receptor antagonist, inhibited D2KATP. ATPi reversibly inhibited D2KATP, with a Ki of 0.212 mM. The Na+-azide- or quinpirole-induced current caused a tolbutamide-sensitive membrane hyperpolarization and a marked reduction in action potential frequency. We propose that ATP-sensitive K+ channels play a metabolism-dependent role in striatal neurons.
Sun
X D
XD
Department of Pharmacology, Pharmacia and Upjohn, Kalamazoo, MI 49007, USA.
Lee
E W
EW
Wong
E H
EH
Lee
K S
KS
D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003342:Corpus Striatum / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004553:Electric Conductivity; D005260:Female; D008297:Male; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019810:Sodium Azide / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
D018491:Dopamine Agonists; D015221:Potassium Channels; D019257:Quinpirole; D000255:Adenosine Triphosphate; D019810:Sodium Azide; D014044:Tolbutamide; D011188:Potassium; D002118:Calcium