PT  - JOURNAL ARTICLE
AU  - Putzier, Ilva
AU  - Kullmann, Paul H. M.
AU  - Horn, John P.
AU  - Levitan, Edwin S.
TI  - Ca<sub>v</sub>1.3 Channel Voltage Dependence, Not Ca<sup>2+</sup> Selectivity, Drives Pacemaker Activity and Amplifies Bursts in Nigral Dopamine Neurons
AID  - 10.1523/JNEUROSCI.4742-09.2009
DP  - 2009 Dec 09
TA  - The Journal of Neuroscience
PG  - 15414--15419
VI  - 29
IP  - 49
4099  - http://www.jneurosci.org/content/29/49/15414.short
4100  - http://www.jneurosci.org/content/29/49/15414.full
SO  - J. Neurosci.2009 Dec 09; 29
AB  - Cav1.3 (α1D) L-type Ca2+ channels have been implicated in substantia nigra (SN) dopamine (DA) neuron pacemaking and vulnerability to Parkinson's disease. These effects may arise from the depolarizing current and cytoplasmic Ca2+ elevation produced by Cav1.3 channels at subthreshold membrane potentials. However, the assumption that the Ca2+ selectivity of Cav1.3 channels is essential has not been tested. In this study the properties of SN DA neuron L-type Ca2+ channels responsible for driving pacemaker activity in juvenile rat brain slices were probed by replacing native channels blocked with the dihydropyridine nimodipine with virtual channels generated by dynamic clamp. Surprisingly, virtual L-type channels that mimic native and recombinant Cav1.3 channels supported pacemaker activity even though dynamic clamp currents are not carried by Ca2+. This effect is specific because pacemaker activity could not be restored by tonic current injection, virtual nonselective leak channels or virtual NMDA receptors, which share with L-type channels a negative slope conductance region in their current–voltage (I–V) curve. Altering virtual channels showed that the production of pacemaker activity depended on the characteristic voltage dependence of DA neuron L-type channels, while activation kinetics and reversal potential were not critical parameters. Virtual L-type channels also supported slow oscillatory potentials and enhanced firing rate during evoked bursts. Thus, Cav1.3 channel voltage dependence, rather than Ca2+ selectivity, drives pacemaker activity and amplifies bursts in SN DA neurons.