A transient potassium conductance regulates the excitability of cultured hippocampal and spinal neurons.
Cultured mouse spinal cord and rat hippocampal neurons were voltage clamped with a two-electrode system in the presence of tetrodotoxin (1 to 3 microM) and tetraethylammonium (25 mM). Depolarizing voltage commands from holding potentials negative to -50 mV evoked a transient outward current response that peaked within 10 msec and decayed exponentially with a time constant of 10 to 40 msec. The current was inactivated by holding at potentials more positive than -50 mV but could be reactivated by brief hyperpolarizing prepulses (20-msec steps to -90 mV reactivated 50%). The inversion potential of the tail current evoked in a double-step protocol was -70 to -75 mV, and this shifted in a depolarizing direction with elevated [K+]0. The transient outward current was blocked by external application of 4-aminopyridine (4-AP) with an IC50 of 2 mM. In experiments under current clamp, 4-AP suppressed an initial transient rectification of the electrotonic potential recorded in response to depolarizing current and reduced the threshold for single and repetitive action potentials. Thus, a transient K+ conductance similar to IA of molluscan neurons may serve to regulate the excitability of some central mammalian neurons. Depression of this conductance by 4-AP could contribute to the drug's convulsant effects in vivo.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002412:Cations; D002478:Cells, Cultured; D004553:Electric Conductivity / Q000187:drug effects; D004622:Embryo, Mammalian; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002412:Cations; D013757:Tetraethylammonium Compounds; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D011188:Potassium