Regulation of somatodendritic dopamine release by corticotropin-releasing factor via the inhibition of voltage-operated Ca2+ channels.

ABSTRACT

Dopamine (DA) neurons in the substantia nigra pars compacta release DA from their somata and dendrites, which regulate motor activity and muscle tone. Previously, we reported that Ca(2+) influx through voltage-operated Ca(2+) channels (VOCCs) contributes to spontaneous somatodendritic DA release. Since corticotropin-releasing factor (CRF) regulates VOCC, we sought to determine whether urocortin affects somatodendritic DA release in the isolated DA neurons using amperometry method. The application of urocortin reversibly inhibited both VOCC and the frequency of DA release events via the activation of type-1 CRF receptor. The blockers for L- and T-type Ca(2+) channels effectively abolished the effects of urocortin both on the frequency of DA release events and on Ca(2+) current. These results indicate that CRF inhibits somatodendritic DA release by inhibiting L- and T-type Ca(2+) channels. Thus, the inhibition of somatodendritic DA release by stress hormone may be one of the molecular mechanisms underlying the effect of stress on motor function.