Differential somatic Ca2+ channel profile in midbrain dopaminergic neurons

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
is indeed higher in the somata of rat SNc DA neurons, and that this current undergoes less
inactivation in this region. Non stationary fluctuation analysis (NSFA) 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
SN 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.