A transient outward current in a mammalian central neurone blocked by 4-aminopyridine

It is becoming increasingly clear that nerve cells in the mammalian central nervous system (CNS) have a very complex electroresponsiveness. They exhibit not only time- and voltage-dependent Na+ and K+ conductances, analogous to those in the squid giant axon1, but also a variety of other conductances that have a significant role in the control of cell excitability. Of the outward currents, there are, in addition to the delayed rectifier, the Ca2+-activated K+ current2,3 which underlies the long-lasting spike afterhyperpolarization, and the M current4, a non-inactivating K+ current evoked by membrane depolarization and blocked by muscarinic, cholinergic agonists. We demonstrate here the existence in a mammalian central neurone (hip-pocampal CA3 pyramidal cells) of yet another outward current, which is transient and may be carried by K+ ions. Further, the experiments show that this current is substantially reduced by the convulsant 4-aminopyridine (4-AP)5, resulting in a marked increase in cell excitability.

[1]  D. A. Brown,et al.  Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone , 1980, Nature.

[2]  K. Krnjević,et al.  EGTA and motoneuronal after‐potentials. , 1978, Journal of Physiology.

[3]  J. L. Kenyon,et al.  4-Aminopyridine and the early outward current of sheep cardiac Purkinje fibers , 1979, The Journal of general physiology.

[4]  T E Spraker,et al.  Cross‐correlation analysis of the maintained discharge of rabbit retinal ganglion cells. , 1981, The Journal of physiology.

[5]  T. Shimahara Modulation of synatpic output by the transient outward potassium current in Aplysia , 1981, Neuroscience Letters.

[6]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[7]  B. Hille The Selective Inhibition of Delayed Potassium Currents in Nerve by Tetraethylammonium Ion , 1967, The Journal of general physiology.

[8]  D. J. Adams,et al.  Ionic currents in molluscan soma. , 1980, Annual review of neuroscience.

[9]  D. Prince,et al.  A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons. , 1980, Journal of neurophysiology.

[10]  H. Jahnsen,et al.  The dendritic response to GABA in CA1 of the hippocampal slice , 1981, Brain Research.

[11]  P. Grafe,et al.  Convulsant actions of 4-aminopyridine on the guinea-pig olfactory cortex slice , 1982, Brain Research.

[12]  C. Stevens,et al.  Voltage clamp studies of a transient outward membrane current in gastropod neural somata , 1971, The Journal of physiology.

[13]  S. Thesleff,et al.  Aminopyridines and synaptic transmission , 1980, Neuroscience.

[14]  S. Thompson Three pharmacologically distinct potassium channels in molluscan neurones. , 1977, The Journal of physiology.

[15]  C. Stevens,et al.  Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma , 1971, The Journal of physiology.

[16]  D. A. Brown,et al.  M-currents in voltage-clamped mammalian sympathetic neurones , 1981, Neuroscience Letters.