Quantification of somatic calcium currents in midbrain dopaminergic neurons

Dopaminergic neurons (DA) within the substantia nigra pars compacta (SNc) and ventral tegmantal area (VTA) are autonomous pacemakers. SNc DA neurons are particularly prone to degeneration in Parkinson’s disease (PD). However, the cause for their high vulnerability to degeneration, compared to the neighboring, more resistant VTA DA neurons, remains unclear. It has been suggested that the pacemaking in SNc DA neurons relies on L-type calcium channels. A large calcium entry through these channels could cause oxidative stress in SNc DA neurons and could explain their vulnerability. We directly tested this hypothesis in young rats by quantifying the density of L-type calcium channels in the soma of DA neurons using nucleated patch-clamp recordings. Our results show measurable L-type (sensitive to 5µM nifedipine) and non L-type calcium currents in the soma of SNc and VTA DA neurons. We found that the amplitude of the nifedipine-sensitive current is higher in SNc DA neurons (17.8±1.6 pA/pF; n=10) than in VTA DA neurons (11.2±1.8 pA/pF; n=10). Interestingly, we noticed that the L-type current is the predominant Ca2+ current in SNc DA neurons (44%) while this is not the case in VTA DA neurons (22%). These results were confirmed by non-stationary-fluctuation analysis (NSFA). These experiments revealed a higher mean number of nifedipine-sensitive Ca2+ channels in the soma of the SNc DA neurons (502±74; n=6) than in VTA DA neurons (160±45; n=6). The greater density of L-type channels in the soma of SNc DA neurons could contribute to their vulnerability in human PD patients