Differential neuromodulation of calcium currents by norepinephrine in rat sympathetic neurons

1. Differences in the neuromodulation of Ca²⁺ currents between superior cervical ganglion (SCG) and more caudal paravertebral ganglion (PVG) neurons acutely isolated from the same rats were investigated using the whole-cell patch-clamp technique. 2. Norepinephrine (NE) induced a concentration- dependent inhibition of Ca²⁺ currents in both SCG and PVG neurons. The concentration producing 50% inhibition (IC₅₀) for NE estimated from concentration-response curves was similar between SCG and PVG neurons but the maximal inhibition estimated from the concentration-response curve for PVG neurons was decreased compared with that of SCG neurons. 3. Tail current activation curves of both SCG and PVG neurons in the absence and presence of NE (5 μM) could be fitted to a double Boltzmann equation. In the presence of NE, the activation curves for both SCG and PVG neurons were shifted toward more depolarized potentials. The magnitude of the shift was greater in SCG than in PVG neurons, which could be accounted for by a greater decrease (P < 0.05) in the fractional amplitude of the first current component of SCG neurons (Δ 1.4 ± 0.4 nA, mean ± SE, 39%) compared with that of PVG neurons (Δ 0.9 ± 0.1 nA, 16%). 4. Ca²⁺ current density, expressed as maximal tail current amplitude normalized to cell capacitance, was greater in PVG neurons than that in SCG neurons. 5. In SCG neurons, a saturating concentration of ω-conotoxin GVIA (ω-CgTx) produced a greater decrease of Ca²⁺ current amplitude at +20 mV (77.4 ± 1.9%) than in PVG neurons (71.2 ± 1.5%, P < 0.05). 6. After pretreatment with 15 μM ω-CgTx, NE still decreased the Ca²⁺ currents in both populations of neurons; however, the inhibition was greater in SCG neurons (31.1 ± 3.4%) than in PVG neurons (12.8 ± 3.6%, P < 0.01). 7. The dihydropyridine Ca²⁺ channel 'agonist' Bay K 8644 (10 μM) prolonged Ca²⁺ tail currents in both SCG and PVG neurons. After normalizing to cell capacitance, there was no significant difference in Bay K 8644- induced tail current amplitude between the two populations of neurons. Moreover, NE (5 μM) increased the prolonged Ca²⁺ tail current amplitude induced by Bay K 8644 (10 μM) by 44.7 ± 13.5% in SCG and 41.9 ± 11.9% in PVG neurons. 8. Under control conditions, Ca²⁺ currents were facilitated by a depolarizing conditioning pulse (50 ms to + 100 mV) in both PVG neurons (29.2 ± 5.1%) and SCG neurons (20.1 ± 4.0%). In the presence of 5 μM NE, however, a greater facilitation was observed in SCG neurons (163.2 ± 19.4%) compared with that in PVG neurons (65.5 ± 9.5%, P < 0.01). 9. Internal dialysis with solutions containing 500 μM guanosine 5'-O-(3- thiotriphosphate) (GTP-γ-S) greatly increased facilitation of Ca²⁺ currents induced by a depolarizing prepulse. However, facilitation was less in PVG neurons (148.8 ± 21.6%) than in SCG neurons (233.7 ± 17.3%, P < 0.01). 10. The differences in the effects of NE on the inhibition of Ca²⁺ currents between SCG and PVG neurons demonstrate heterogeneous neuromodulation of neuronal Ca²⁺ currents. A difference in functional G- protein availability or defective G-protein effector coupling may be major factors that contribute to the differential neuromodulation of Ca²⁺ currents in different populations of sympathetic neurons.