Intracellular effects of QX-314 and Cs+ in hippocampal pyramidal neurons in vivo

The effects of intracellular diffusion of the lidocaine derivative anesthetic QX-314 and of Cs+, which block Na+ and K+ conductances, respectively, were investigated in vivo in rat CA1 and CA3 pyramidal neurons to demonstrate slow Ca(2+)-related events. QX-314 loading prevented fast Na+ spikes, but slower presumably Ca2+ spikes remained. A slower and a faster duration type of QX-314-resistant spikes were observed. The former had high thresholds, while the latter was activated at moderate depolarized levels. The slower and the faster QX-314-resistant spikes fired at frequencies up to 8/s and 35/s and were 35-60 and 5-10 ms in duration, respectively. With Cs+ loading, pyramidal neurons depolarized and slow, presumably Ca2+, and fast Na+ spikes widened. Fast spikes usually showed a prominent shoulder and a slower repolarization. No differences were observed between drug effects in CA1 and CA3 neurons. In terms of their possible participation in theta rhythm genesis the slow QX-314-resistant events display the correct frequency and duration and can oscillate regeneratively.

[1]  R. Llinás,et al.  Electrophysiology of mammalian inferior olivary neurones in vitro. Different types of voltage‐dependent ionic conductances. , 1981, The Journal of physiology.

[2]  D. Prince,et al.  Participation of calcium spikes during intrinsic burst firing in hippocampal neurons , 1978, Brain Research.

[3]  R. Miles,et al.  Intracellular fluoride alters the kinetic properties of calcium currents facilitating the investigation of synaptic events in hippocampal neurons , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  Yosef Yarom,et al.  Low threshold calcium spikes, intrinsic neuronal oscillation and rhythm generation in the CNS , 1989, Journal of Neuroscience Methods.

[5]  D. Johnston,et al.  Voltage clamp discloses slow inward current in hippocampal burst-firing neurones , 1980, Nature.

[6]  A. Alonso,et al.  Evidence for separate projections of hippocampal pyramidal and non-pyramidal neurons to different parts of the septum in the rat brain , 1982, Neuroscience Letters.

[7]  R. Llinás,et al.  Properties and distribution of ionic conductances generating electroresponsiveness of mammalian inferior olivary neurones in vitro. , 1981, The Journal of physiology.

[8]  A. Nuñez,et al.  Slow intrinsic spikes recorded in vivo in rat CA1–CA3 hippocampal pyramidal neurons , 1990, Experimental Neurology.

[9]  B. MacVicar Depolarizing prepotentials are Na+ dependent in CA1 pyramidal neurons , 1985, Brain Research.

[10]  R K Wong,et al.  Afterpotential generation in hippocampal pyramidal cells. , 1981, Journal of neurophysiology.

[11]  W. Bun˜o,et al.  Intracellular θ-rhythm generation in identified hippocampal pyramids , 1987, Brain Research.

[12]  William A. Catterall,et al.  Clustering of L-type Ca2+ channels at the base of major dendrites in hippocampal pyramidal neurons , 1990, Nature.

[13]  D. Prince,et al.  Electrophysiology of isolated hippocampal pyramidal dendrites , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  L. A. Gay,et al.  Cs+ causes a voltage-dependent block of inward K currents in resting skeletal muscle fibres , 1977, Nature.

[15]  D. Mogul,et al.  Evidence for multiple types of Ca2+ channels in acutely isolated hippocampal CA3 neurones of the guinea‐pig. , 1991, The Journal of physiology.

[16]  A. Ogura,et al.  Three types of voltage-dependent calcium current in cultured rat hippocampal neurons , 1989, Brain Research.

[17]  B. Connors,et al.  Effects of local anesthetic QX-314 on the membrane properties of hippocampal pyramidal neurons. , 1982, The Journal of pharmacology and experimental therapeutics.

[18]  W Buño,et al.  Septo-hippocampal relationships during EEG theta rhythm. , 1982, Electroencephalography and clinical neurophysiology.

[19]  R. Llinás,et al.  Ionic basis for the electro‐responsiveness and oscillatory properties of guinea‐pig thalamic neurones in vitro. , 1984, The Journal of physiology.