Calcium spike underlying rhythmic firing in dopaminergic neurons of the rat substantia nigra

Neurosci Res. 1993 Dec;18(3):195-207. doi: 10.1016/0168-0102(93)90055-u.


In order to study a possible mechanism for rhythmic firing of dopaminergic (DA) neurons, intracellular recordings were obtained from 56 rhythmically firing DA neurons in the rat substantia nigra compacta (SNc), using in vitro slice preparations. In the presence of TTX, spontaneous oscillation of the membrane potential was induced in SNc DA neurons when the membrane potential was depolarized more positive from -60 to -40 mV. Each oscillation wave was characterized by a pacemaker-like slow depolarization (PLSD) followed by a relatively prompt repolarization. As the DC depolarization was increased from -60 to -40 mV, the oscillation frequency increased from 0.5 to 5 Hz, but the amplitude of the wave decreased. Of 17 neurons tested in the presence of TTX, the maximum amplitudes of the oscillation varied from 10-15 mV in 8 neurons and were less than 5 mV in 9 neurons. In those 9 neurons, an application of TEA greatly enhanced (up to 15 mV) the amplitude of oscillation. The oscillation ceased when the membrane was hyperpolarized more negative than -60 mV. At the membrane potential more negative than -60 mV in the presence of TTX an injection of a depolarizing current pulse could evoke PLSD which was an all-or-nothing regenerative spike potential. The rate of rise of the PLSD changed depending on the intensity of injected current pulses but their amplitude remained constant. Its time-to-peak was slow (up to 1400 ms), while the decay time was relatively brief (< 500 ms). The threshold membrane potential for evoking PLSD was -53.7 +/- 3.2 mV (n = 10). This was higher than the previously reputed threshold for low threshold Ca2+ spike (LTS) (< -60 mV) and lower than that for high threshold Ca2+ spike (HTS) (> -35 mV) in SNc DA neurons. Even at a holding potential of -45 mV, a depolarizing current pulse could trigger PLSD while LTS was completely inactivated. Cd2+ (0.4 mM) abolished the oscillation and PLSD without marked effects on the LTS (n = 6). A low Ca2+ and high Mg2+ Ringer's solution also abolished the oscillation and PLSD (n = 4). An intracellular injection of EGTA markedly prolonged the decay time course of PLSD characterized by a slow and a relatively fast falling phase (n = 5). This would suggest an involvement of Ca(2+)-dependent K+ conductance and/or Ca2+ dependent inactivation of Ca2+ conductance during repolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Calcium / physiology*
  • Dopamine / physiology*
  • Electrophysiology
  • Immunohistochemistry
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons / physiology*
  • Phenotype
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / cytology
  • Substantia Nigra / physiology*
  • Tetrodotoxin / pharmacology
  • Tyrosine 3-Monooxygenase / immunology
  • Tyrosine 3-Monooxygenase / metabolism


  • Tetrodotoxin
  • Tyrosine 3-Monooxygenase
  • Calcium
  • Dopamine