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 microM) 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 (delta 1.4 +/- 0.4 nA, mean +/- SE, 39%) compared with that of PVG neurons (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 microM omega-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 microM) 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 microM) increased the prolonged Ca2+ tail current amplitude induced by Bay K 8644 (10 microM) 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%).(ABSTRACT TRUNCATED AT 400 WORDS)
Chen
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Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Schofield
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004558:Electric Stimulation; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D010455:Peptides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020866:omega-Conotoxin GVIA; D019204:GTP-Binding Proteins; D009638:Norepinephrine