Diazoxide suppresses slowly-inactivating outward and inward currents in CA1 hippocampal neurones

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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.

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