Influence of R-type (Ca(v)2.3) and T-type (Ca(v)3.1-3.3) 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 muM of the Ca(v)2.3 inhibitor SNX-482, or 100 muM of mibefradil, decreased the concentrations of dopamine and its metabolites in dialysate from substantia nigra, whereas 1 muM mibefradil or 40-80 muM nickel(II) induced an increase in nigral dialysate dopamine concentrations. Dopamine concentrations in striatal dialysates were decreased only by 10 muM of SNX-482 or 100 muM 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 Cav3.1-3.3 (T-type) channels. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.