PDZ (PSD-95/Disc large/Zonula occludens-1) domains are protein interaction motifs. They bind specific cytoplasmatic C-termini of target proteins, which are present in diverse transmembrane receptors and channels. In order to identify new interaction partners regulating the activity of the voltage-gated Ca²⁺ channel Ca_v1.2 and of the plasma membrane Ca²⁺ ATPase isoform 4b, we used PDZ domain arrays testing for 100 different PDZ domains, GST pull-downs and conventional immunoprecipitation assays. In the PDZ array, strongest interactions for Ca_v1.2 and PMCA4b were found for the PDZ domains of SAP-102; MAST-205; MAGI-3; OMP25 and ZO-1. Additionally, we established interactions between Ca_v1.2 and the PDZ domains of NHERF1; PIST and PMCA4b with Chapsyn-110; CASK and AIP1, whereas the formerly described interaction of PMCA4b with Chapsyn-110 and CASK was confirmed. A further focus was to demonstrate interaction of Ca_v1.2 and PMCA4b with MAST-205 and MAGI-3 via GST pull-down and immunoprecipitation. We also verified the direct interaction of the C-terminus of Ca_v1.2 and the PDZ domain of nNOS. The hypothesis suggested that nNOS overexpression reduces Ca²⁺ influx over Ca_v1.2. To address this question, we measured Ca²⁺ currents in Xenopus oocytes expressing the Ca_v1.2, the nNOS, the beta 3 subunit of voltage gated calcium channel or combinations of these. From our results we conclude that Ca_v1.2 and PMCA4b bind promiscuously to a variety of PDZ domains. However, the physiological consequence of some of these interactions remains to be investigated.