Differential Somatic Ca2+ Channel Profile in Midbrain Dopaminergic Neurons

作者：Philippart Fabian; Destreel Geoffrey; Merino Sepulveda Paulina; Henny Pablo; Engel Dominique; Seutin Vincent^*

来源：Journal of Neuroscience, 2016, 36(27): 7234-7245.

DOI：10.1523/JNEUROSCI.0459-16.2016

• action potential clamp
• dopaminergic neurons
• neurodegeneration
• nonstationary fluctuation analysis
• nucleated patches
• voltage-dependent calcium channels

Dopaminergic (DA) neurons located in the ventral midbrain continuously generate a slow endogenous pacemaker activity, the mechanism of which is still debated. It has been suggested that, in the substantia nigra pars compacta (SNc), the pacemaking relies more on Ca2+ channels and that the density of L-type Ca2+ channels is higher in these DA neurons than in those located in the ventral tegmental area (VTA). This might lead to a higher Ca2+ load in SNc DA neurons and explain their higher susceptibility to degeneration. However, direct evidence for this hypothesis is lacking. We found that the L-type current and channel density are indeed higher in the somata of rat SNc DA neurons and that this current undergoes less inactivation in this region. Nonstationary fluctuation analysis measurements showed a much higher number of L-type channels in the soma of SNc DA neurons, as well as a smaller single-channel conductance, pointing to a possible different molecular identity of L-type channels in DA neurons from the two areas. A major consequence of this is that pacemaking and, even more so, bursting are associated with a larger Ca2+ entry through L-type channels in SNc DA neurons than in their VTA counterparts. Our results establish a molecular and functional difference between two populations of midbrain DA neurons that may contribute to their differential sensitivity to neurodegeneration.

• 出版日期2016-7-6