Calcium influx through Ca_V1.2 induces PKA-II activity during depolarization. (A) Expression pattern of VGCC α subunits in overnight cultures of rat and mouse DRG determined by RNA-seq (Isensee et al., 2014b). TPM, transcripts per kilobase million. (B) Expression pattern of VGCC α subunits in mouse DRG neuron subgroups determined by single-cell RNA-seq (Zeisel et al., 2018). (C) Time course of pRII intensity in KCl-depolarized rat sensory neurons after pretreatment (10 min) with the NMDA receptor antagonist D-AP5 (10 µM), the Cav3.1-3.3 blocker TTA-P2 (1 µM), and a combination of the Cav2.1/2.2 blocker ω-agatoxin IVA (100 nM), ω-conotoxin MVIIC (200 nM), and ω-conotoxin GVIA (1 µM). (D) Inhibitory effect of verapamil (20 or 200 µM, 10-min pretreatment) on the pRII increase induced by KCl depolarization. (E) Dose–response curve showing the effect of verapamil (0–200 µM; IC₅₀ = 16 µM) on pRII signals induced by KCl depolarization (3 min). (F) Inhibitory effect of diltiazem (100 µM, 10 min) on the KCl-induced pRII increase. (G) Dose–response curve showing the inhibition of KCl-induced pRII signals by diltiazem (0–200 µM; IC₅₀ = 37 µM). (H) Reinforcing effect of the Ca_V1 agonist (S)-(-)-Bay K 8644 (2 µM, 10 min) on pRII signals induced by a low dose of KCl (10 mM). (I) Dose–response curve showing the reinforcing effect of Bay K 8644 (0–5 µM; EC₅₀ = 80 nM) on pRII signals induced by KCl (10 mM, 3 min). (J) Chelation of extracellular calcium with EGTA (2.5 mM, 30-min prestimulation) abolished the pRII response to KCl-depolarization. (K) Effect of the cell-permeable calcium chelator BAPTA-AM (100 µM, 60 min) on pRII signals induced by KCl depolarization (compound effect: F_1,28 = 10.9, P < 0.003). Values in C–K represent means ± SEM; n = 3–4 experiments; >2,000 neurons/condition; two-way ANOVA with Bonferroni’s test; ^§, P < 0.05; ^§§, P < 0.01; ^§§§, P < 0.001 indicate significance levels between KCl-induced pRII signals in the absence or presence of an agonist/antagonist.