Influence of R-type (Cav2.3) and t-type (Cav3.1-3.3) antagonists on nigral somatodendritic dopamine release measured by microdialysis

Neuroscience. 2003;120(3):757-64. doi: 10.1016/s0306-4522(03)00385-3.

Abstract

The release of dopamine from soma and dendrites of dopaminergic neurons in substantia nigra has been reported to be calcium-dependent, but it remains to be determined which calcium channels mediate this effect. We have used in vivo microdialysis in rat substantia nigra and striatum to investigate the effect of Ca(v)3.1-3.3 (T-type) and Ca(v)2.3 (R-type) calcium channel antagonists on somatodendritic and terminal dopamine release. Local reverse dialysis administration of 0.1-10 microM of the Ca(v)2.3 inhibitor SNX-482, or 100 microM of mibefradil, decreased the concentrations of dopamine and its metabolites in dialysate from substantia nigra, whereas 1 microM mibefradil or 40-80 microM nickel(II) induced an increase in nigral dialysate dopamine concentrations. Dopamine concentrations in striatal dialysates were decreased only by 10 microM of SNX-482 or 100 microM of mibefradil. Nickel(II) induced an increase in striatal dialysate dopamine concentration similar to that in substantia nigra. The results indicate a role for Ca(v)2.3 (R-type) voltage sensitive calcium channels in the calcium dependency of somatodendritic dopamine release, but argue against a calcium dependency mediated substantially by Ca(v)3.1-3.3 (T-type) channels.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, R-Type / metabolism*
  • Calcium Channels, T-Type / metabolism*
  • Dendrites / drug effects*
  • Dendrites / metabolism*
  • Dopamine / metabolism*
  • Homovanillic Acid / metabolism
  • Male
  • Microdialysis
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism*

Substances

  • Calcium Channel Blockers
  • Calcium Channels, R-Type
  • Calcium Channels, T-Type
  • 3,4-Dihydroxyphenylacetic Acid
  • Dopamine
  • Homovanillic Acid