Identification of an ATP-sensitive K+ channel in rat cultured cortical neurons.
To determine whether membranes of mammalian central neurons contain an ATP-sensitive K+ (KATP) channel similar to that present in pancreatic beta cells, the patch-clamp technique was applied to cultured neurons prepared from the neonatal rat cerebral cortex and hippocampus. In whole-cell experiments with hippocampal neurons, extracellular application of 0.5 mM diazoxide (a KATP channel activator) elicited a hyperpolarization concomitant with an increase in membrane conductance, whereas application of 0.5 mM tolbutamide (a KATP channel blocker) induced a depolarization with a decrease in conductance. Similar results were obtained with cortical neurons. In outside-out patch experiments with cortical neurons, a K+ channel sensitive to these drugs was found. The channel was completely blocked by 0.5 mM tolbutamide and activated by 0.5 mM diazoxide. The single-channel conductance was 65 pS under symmetrical 145 mM K+ conditions and 24 pS in a physiological K+ gradient. In inside-out patch experiments, this channel was demonstrated to be inhibited by an application of 0.2-1 mM ATP to the cytoplasmic surface of the patch membrane. These results indicate that the membranes of rat cortical neurons contain a KATP channel that is quite similar to that found in pancreatic beta cells. It is also suggested that the same or a similar K+ channel may exist in membranes of hippocampal neurons.
Ohno-Shosaku
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T
Department of Physiology, Faculty of Medicine, Kanazawa University, Japan.
Yamamoto
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C
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D003981:Diazoxide / Q000494:pharmacology*; D004553:Electric Conductivity / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D014044:Tolbutamide / Q000494:pharmacology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D003981:Diazoxide