Pre- and postsynaptic ATP-sensitive potassium channels during metabolic inhibition of rat hippocampal CA1 neurons.
Presynaptic and postsynaptic membrane activities during experimental metabolic inhibition were analysed in mechanically dissociated rat hippocampal neurons using nystatin-perforated and conventional whole-cell patch clamp recordings. NaCN, an inhibitor of mitochondrial ATP synthesis, induced an outward current across the postsynaptic soma membrane. This current was blocked by tolbutamide, a sulfonylurea, which blocks ATP-sensitive K+ (KATP) channels. The presynaptic effect of metabolic inhibitors such as NaCN, NaN3, or glucose-free solution was to increase the frequency of GABAergic miniature inhibitory postsynaptic currents (mIPSCs). Tolbutamide had no effect on this increase in mIPSC frequency induced by metabolic inhibition. Diazoxide, a KATP channel opener, evoked a similar somatic outward current in a dose-dependent manner. In addition, diazoxide decreased the frequency of mIPSCs in a dose-dependent fashion. Both these pre- and postsynaptic effects of diazoxide were reversed by tolbutamide, suggesting the existence of KATP channels on both pre- and postsynaptic membranes. These results confirm the presence of KATP channels on both the pre- and postsynaptic membranes but indicate that the channels have significantly different sensitivities to metabolic inhibition.
Matsumoto
Nozomu
N
Cellular and System Physiology, Graduate School of Medical Sciences and Department of Otolaryngology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Komiyama
Sohtaro
S
Akaike
Norio
N
D018528:ATP-Binding Cassette Transporters; D000465:Algorithms; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D054086:KATP Channels; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D012966:Sodium Cyanide / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018528:ATP-Binding Cassette Transporters; D000963:Antimetabolites; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011963:Receptors, GABA-A; D017661:Receptors, Presynaptic; C092520:uK-ATP-1 potassium channel; D005680:gamma-Aminobutyric Acid; D012966:Sodium Cyanide