Whole-cell patch clamp techniques were used to examine neurokinin receptor modulation of Ca²⁺ channels in small dorsal root ganglia neurons (< 40 pF) which express mainly N- and L-type Ca²⁺ currents. Low concentrations of substance P enhanced Ca²⁺ currents (5-40%, <0.2 µM) or while higher concentrations applied cumulatively reversed these enhancements (5-28% reductions, >0.5 µM). This apparent inhibition by high concentrations of substance P was blocked by the administration of the NK₃ antagonist SB 235,375 (0.2 µM). The NK₁ agonist, [Sar⁹, Met¹¹]-substance P (0.05 to 1.0) µM did not alter Ca²⁺ currents; whereas the NK₂ agonist, [Ala⁸]-neurokinin A (4-10), enhanced Ca²⁺ currents (5-36% increase, 0.05-0.5 µM). The enhancement was reversed by the NK₂ antagonist MEN 10,376 (0.2 µM) but unaffected by the NK₃ antagonist SB 235,375 (0.2 µM). The NK₃ agonist [MePhe⁷]-neurokinin B (0.5-1.0 µM) inhibited Ca²⁺ currents (6-24% decrease). This inhibition was not prevented by the NK₂ antagonist MEN 10,376 (0.2 µM) but was blocked by the NK₃ antagonist SB 235,375 (0.2 µM). Both the enhancement and inhibition of Ca²⁺ currents by neurokinin agonists were reversed by the protein kinase C inhibitor bisindolylmaleimide I HCl (0.2-0.5 µM). Following inhibition of Ca²⁺ channels by [MePhe⁷]-neurokinin the facilitatory effect of BayK 8644(5 µM) was increased and the inhibitory effect of the N-type Ca²⁺ channel blocker -conotoxin GVIA (1 µM) was diminished, suggesting that the NK₃ agonist inhibits N-type Ca²⁺ channels. Similarly, block of all but N-type Ca²⁺ channels, revealed that [Ala⁸]-neurokinin A (4-10) enhanced the currents while [MePhe⁷]-neurokinin B inhibited the currents. Inhibition of all but L-type Ca²⁺ channels, revealed that [Ala⁸]-neurokinin A (4-10) enhanced the currents while [MePhe⁷]-neurokinin B had no effect. Activation of protein kinase C with low concentrations of phorbol-12,13-dibutyrate enhanced Ca²⁺ currents, but high concentrations inhibited N- and L-type Ca²⁺ currents. In summary, these data suggest that in adult rat dorsal root ganglia neurons, NK₂ receptors enhance both L- and N-type Ca²⁺ channels and NK₃ receptors inhibit N-type Ca²⁺ channels and that these effects are mediated by protein kinase C phosphorylation of Ca²⁺ channels.