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.