Wang, J (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 115 Life Sci Addit, Berkeley, CA 94720 USA,
Glial cell line-derived neurotrophic factor (GDNF) is best known for its long-term survival effect on dopaminergic neurons in the ventral midbrain. A recent study showed that acute application of GDNF to these neurons suppresses A-type potassium channels and potentiates neuronal excitability. Here we have characterized the acute effects of GDNF on Ca2+ channels and synaptic transmission. GDNF rapidly and reversibly potentiated the high voltage-activated (HVA) Ca2+ channel currents in cultured dopaminergic neurons. Analyses of channel kinetics indicate that GDNF decreased the activation time constant, increased the inactivation and deactivation time constants of HVA Ca2+ channel currents. Ca2+ imaging experiments demonstrate that GDNF facilitated Ca2+ influx induced by membrane depolarization. To investigate the physiological consequences of the Ca2+ channel modulation, we examined the acute effects of GDNF on excitatory synaptic transmission at synapses made by these dopaminergic neurons, which co-release the transmitter glutamate. Within 3 min of application, GDNF increased the amplitude of spontaneous and evoked excitatory autaptic- or multiple-postsynaptic currents. The frequency as well as the amplitude of miniature excitatory postsynaptic currents was also increased. These results reveal, for the first time, an acute effect of GDNF on synaptic transmission and its potential mechanisms, and suggest that an important function of GDNF for midbrain dopaminergic neurons is the acute modulation of transmission and ion channels. Copyright (C) 2003 S. Karger AG, Basel.