Influence of R-type (Cav2.3) and t-type (Cav3.1-3.3) antagonists on nigral somatodendritic dopamine release measured by microdialysis.
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.
Bergquist
F
F
Institute of Physiology and Pharmacology, Department of Pharmacology, Göteborg University, Box 431, Medicinargatan 15D, 405 30 Göteborg, Sweden. filip.berquist@pharm.gu.se
Nissbrandt
H
H
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020908:Calcium Channels, R-Type / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism*
D002121:Calcium Channel Blockers; D020908:Calcium Channels, R-Type; D020747:Calcium Channels, T-Type; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid