In the central nervous system, L-type voltage gated calcium channels (LTCCs) come in two isoforms, namely Ca_v1.2 and Ca_v1.3 channels. It has been shown previously that these channels differ in biophysical properties, subcellular localization and in the coupling to the gene transcription machinery. In previous work on rat hippocampal neurons we have identified an excitatory cation conductance and an inhibitory potassium conductance as important LTCC coupling partners. Notably, a stimulus-dependent interplay of LTCC-mediated Ca²⁺ influx and activation of these Ca²⁺-dependent conductances was found to give rise to characteristic voltage responses. However, the contribution of Ca_v1.2 and Ca_v1.3 to these voltage responses remained unknown. Hence, the relative contribution of the LTCC isoforms therein was the focus of the current study on hippocampal neurons derived from genetically modified mice, which either lack a LTCC isoform (Ca_v1.3 knock-out mice) or express a dihydropyridine-insensitive LTCC isoform (Ca_v1.2DHP-- knock-in mice). We identified common and alternate ion channel couplings of Ca_v1.2 and Ca_v1.3 channels. Whereas hyperpolarizing Ca²⁺-dependent conductances were coupled to both Ca_v1.2 and Ca_v1.3 channels, an afterdepolarizing potential was only induced by the activity of Ca_v1.2 channels. Unexpectedly, the activity of Ca_v1.2 channels was found at relatively hyperpolarized membrane voltages. Our data add important information about the differences between Ca_v1.2 and Ca_v1.3 channels, that furthers our understanding of the physiological and pathophysiological neuronal roles of these calcium channels. Moreover, our findings suggest that Ca_v1.3 knock-out mice together with Ca_v1.2DHP-- knock-in mice provide valuable models for future investigation of hippocampal LTCC-dependent afterdepolarizations.