Isradipine, a clinically approved L-type calcium channel inhibitor, is currently used in a clinical trial in order to slow the progression of Parkinson disease (PD-Steady III). Although there is in vitro evidence that isradipine reduces activity-dependent calcium loading of dopamine (DA) substantia nigra (SN) neurons, it is however unknown whether isradipine affects the in vivo activity of DA SN neurons in therapeutically relevant concentrations. We have previously presented evidence for a selective role of isradipine-sensitive L-type calcium channels in boosting in vitro burst excitability in lateral but not in medial DA SN neurons of adult C57Bl6N mice (Shin et al., SfN 2017). To now probe for a role of isradipine in the therapeutically relevant, low nanomolar concentration range in controlling in vivo bursting of DA SN neurons, we carried out single unit recordings of DA SN neurons combined with juxtacellular labeling in anesthetized mice. Systemic applications of 3 mg/kg isradipine (i.p.) resulted in a selective reduction of in vivo bursting of lateral DA SN neurons (spikes fired in bursts: control, 41.84 ± 26.48 %, isradipine, 25.69 ± 23.03 %, n=18, p=0.0006), while firing properties of medial DA SN neurons remained unaffected (spikes fired in bursts: control, 14.63 ± 18.67 %, isradipine, 14.65 ± 16.08 %, n=17, p=0.94). The maximal in vivo effect on bursting was observed at about 15 minutes after systemic drug application, which corresponded to a free plasma concentration of ca. 3 nM isradipine (22.53 ± 3.26 ng/ml at 15 min. post-injection, assuming 95% plasma protein binding, n=5). In vitro bath application of 3 nM isradipine was sufficient to induce a partial inhibition of burst excitability in lateral DA SN neurons (gain: control, 758.3 ± 120.3 Hz*nS, n=24, 300 nM isradipine, 425.9 ± 106.5 Hz*nS, n=17, 3 nM isradipine, 641 ± 181.8 Hz*nS, n=14) consistent with our in vivo results. We are currently probing for behavioral effects of low nanomolar isradipine locally infused into the lateral SN of freely moving mice to identify behavioral consequences of acutely suppressed burst activity in lateral SN DA neurons. In summary, our data identify a surprisingly selective effect of low nanomolar isradipine on burst firing of lateral SN DA neurons, which are the most vulnerable DA subpopulation in Parkinson disease.