DIFFERENTIAL NEUROMODULATION OF CALCIUM CURRENTS BY NOREPINEPHRINE INRAT SYMPATHETIC NEURONS

1. Differences in the neuromodulation of Ca2+ currents between superio r cervical ganglion (SCG) and more caudal paravertebral ganglion (PVG) neurons acutely isolated from the same rats were investigated using t he whole-cell patch-clamp technique. 2. Norepinephrine (NE) induced a concentration-dependent inhibition of Ca2+ currents in both SCG and PV G neurons. The concentration producing 50% inhibition (IC50) for NE es timated from concentration-response curves was similar between SCG and PVG neurons but the maximal inhibition estimated from the concentrati on-response curve for PVG neurons was decreased compared with that of SCG neurons. 3. Tail current activation curves of both SCG and PVG neu rons in the absence and presence of NE (5 muM) could be fitted to a do uble Boltzmann equation. In the presence of NE, the activation curves for both SCG and PVG neurons were shifted toward more depolarized pote ntials. The magnitude of the shift was greater in SCG than in PVG neur ons, which could be accounted for by a greater decrease (P < 0.05) in the fractional amplitude of the first current component of SCG neurons (DELTA 1.4 +/- 0.4 nA, mean +/- SE, 39%) compared with that of PVG ne urons (DELTA 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 omega-conotoxin GVIA (omega-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 muM omega-CgTx, NE still decreased the Ca2+ currents in both populations of neurons; however, the inhibition was greater in SCG neu rons (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 muM) prol onged Ca2+ tail currents in both SCG and PVG neurons. After normalizin g to cell capacitance, there was no significant difference in Bay K 86 44-induced tail current amplitude between the two populations of neuro ns. Moreover, NE (5 muM) increased the prolonged Ca2+ tail current amp litude induced by Bay K 8644 (10 muM) 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 muM NE, however, a greater facilitation was o bserved in SCG neurons (163.2 +/- 19.4%) compared with that in PVG neu rons (6 5.5 +/- 9.5%, P < 0.01). 9. Internal dialysis with solutions c ontaining 500 muM guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) gr eatly increased facilitation of Ca2+ currents induced by a depolarizin g prepulse. However, facilitation was less in PVG neurons (148.8 +/- 2 1.6%) than in SCG neurons (233.7 +/- 17.3%, P < 0.01). 10. The differe nces in the effects of NE on the inhibition of Ca2+ currents between S CG and PVG neurons demonstrate heterogeneous neuromodulation of neuron al Ca2+ currents. A difference in functional G-protein availability or defective G-protein effector coupling may be major factors that contr ibute to the differential neuromodulation of Ca2+ currents in differen t populations of sympathetic neurons.