Nifedipine- and omega-conotoxin-sensitive Ca2+ conductances in guinea-pig substantia nigra pars compacta neurones

J Physiol. 1993 Jul:466:727-47.

Abstract

1. The membrane properties of substantia nigra pars compacta (SNc) neurones were recorded in guinea-pig in vitro brain slices. 2. In the presence of tetrodotoxin (TTX) a Ca(2+)-dependent slow oscillatory potential (SOP) was generated. Application of 0.5-20 microM nifedipine abolished both spontaneous and evoked SOPs. A tetraethylammonium chloride (TEA)-promoted high-threshold Ca2+ spike (HTS) was little affected by nifedipine. On the other hand, omega-conotoxin applied either locally or via the perfusion medium (1-10 microM) blocked a part of the HTS, but it did not alter the SOP. 3. In normal medium nifedipine blocked the spontaneous discharge, decreased the interspike interval (ISI) recorded during depolarizing current injections and selectively reduced the slow component of the spike after-hyperpolarization (AHP). omega-Conotoxin decreased both the rising and falling slopes of the normal action potential, reduced the peak amplitude of the spike AHP, and, in some of the neurones, reduced the ISI during depolarization. The Na+ spikes recorded in Ca(2+)-free medium were not altered by omega-conotoxin. 4. The SOP was not blocked by octanol (100-200 microM), amiloride (100-250 microM), or Ni2+ (100-300 microM). However, at 500 microM Ni2+ attenuated the SOP. 5. Application of apamin (0.5-2.0 microM) induced irregular firing or bursting, abolished the slow component of the spike AHP and reduced its peak amplitude. In the presence of TTX and apamin long-duration plateau potentials occurred, which were subsequently blocked by nifedipine. 6. In Ca(2+)-free, Co(2+)-containing medium TTX-sensitive spikes and voltage plateaux were generated by depolarizing current pulses. It is suggested that a persistent Na+ conductance underlies the plateaux, which may be co-activated during the SOP. 7. The results suggest that the Ca2+ currents underlying the SOP and the HTS are different and that they activate at least two Ca(2+)-dependent K+ conductances. These conductances play major roles in the maintenance of spontaneous discharge and in control of membrane excitability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Apamin / pharmacology
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / classification
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Electric Conductivity
  • Evoked Potentials / drug effects
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Mollusk Venoms / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism
  • Nifedipine / pharmacology*
  • Peptides / pharmacology*
  • Substantia Nigra / cytology
  • Substantia Nigra / metabolism*
  • Tetraethylammonium
  • Tetraethylammonium Compounds / pharmacology
  • Tetrodotoxin / pharmacology
  • omega-Conotoxin GVIA

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Mollusk Venoms
  • Peptides
  • Tetraethylammonium Compounds
  • Apamin
  • Tetrodotoxin
  • Tetraethylammonium
  • omega-Conotoxin GVIA
  • Nifedipine
  • Calcium