Diazoxide suppresses slowly-inactivating outward and inward currents in CA1 hippocampal neurones.
Diazoxide (DZX) opens ATP-sensitive K (KATP) channels in muscle and other cells. In whole-cell voltage-clamp recordings in slices, in the presence of kynurenate and bicuculline to minimize indirect effects, DZX (0.65 mM) did not increase input conductance; but it sharply reduced persistent inward and outward currents. An inward current (peak near -20 mV) was especially clear in the presence of K channel blockers; was fully evident in Ca-channel blocking medium; but was abolished by tetrodotoxin. The main direct effects of DZX on these neurones are thus mediated not by activation of KATP channels, but rather by modulation of voltage-dependent channels, including a TTX-sensitive persistent NA current and possibly a Ca current.
Erdemli
G
G
Anaesthesia Research Department, McGill University, Montréal, Québec, Canada.
Krnjević
K
K
D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015221:Potassium Channels; D015222:Sodium Channels; D013779:Tetrodotoxin; D003981:Diazoxide; D002118:Calcium