Dantrolene depolarizes hippocampal neurons in slices from rats.
In intracellular recordings by current clamp, dantrolene (sodium salt, 20 microM) regularly depolarized CA1 neurons (by approximately 13 mV), even in the presence of tetrodotoxin. Dantrolene almost abolished slow (but not medium) afterhyperpolarizations (AHP) (down by approximately 80%). As in previous experiments, dantrolene strongly depressed the hyperpolarization and resistance drop caused by hypoxia. Under voltage clamp (at approximately -70 mV), dantrolene accordingly elicited an inward current of approximately -100 pA and suppressed a voltage-dependent slow outward current and tail current, as well as the outward current generated by hypoxia. In addition, dantrolene enhanced Q-current (IQ) inward relaxations; but it had no effect on high voltage activated Ca currents and did not prevent their suppression by hypoxia. We conclude that depression of slow AHP current and increase in IQ probably account for the depolarizing action of dantrolene.
Krnjević
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Anaesthesia Research Department, McGill University, Montréal, Canada.
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D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D003620:Dantrolene / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D002534:Hypoxia, Brain / Q000503:physiopathology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D015220:Calcium Channels; D009125:Muscle Relaxants, Central; D003620:Dantrolene