Low voltage activation of Ca V1.3 L-type Ca 2+ channels controls excitability in sensory cells and central neurons as well as sinoatrial node pacemaking. Ca V1.3-mediated pacemaking determines neuronal vulnerability of dopaminergic striatal neurons affected in Parkinson disease. We have previously found that in Ca V1.4 L-type Ca 2+ channels, activation, voltage, and calcium-dependent inactivation are controlled by an intrinsic distal C-terminal modulator. Because alternative splicing in the Ca V1.3 α1 subunit C terminus gives rise to a long (Ca V1.3 42) and a short form (Ca V1.3 42A), we investigated if a C-terminal modulatory mechanism also controls Ca V1.3 gating. The biophysical properties of both splice variants were compared after heterologous expression together with β3 and α2δ1 subunits in HEK-293 cells. Activation of calcium current through Ca V1.3 42A channels was more pronounced at negative voltages, and inactivation was faster because of enhanced calcium-dependent inactivation. By investigating several Ca V1.3 channel truncations, we restricted the modulator activity to the last 116 amino acids of the C terminus. The resulting Ca V1.3 ΔC116 channels showed gating properties similar to Ca V1.3 42A that were reverted by co-expression of the corresponding C-terminal peptide C 116. Fluorescence resonance energy transfer experiments confirmed an intramolecular protein interaction in the C terminus of Ca V1.3 channels that also modulates calmodulin binding. These experiments revealed a novel mechanism of channel modulation enabling cells to tightly control Ca V1.3 channel activity by alternative splicing. The absence of the C-terminal modulator in short splice forms facilitates Ca V1.3 channel activation at lower voltages expected to favor Ca V1.3 activity at threshold voltages as required for modulation of neuronal firing behavior and sinoatrial node pacemaking.