Norepinephrine inhibits calcium currents and EPSPs via a G-protein-coupled mechanism in olfactory bulb neurons.
The most pronounced effect of norepinephrine (NE) in the olfactory bulb is disinhibition of mitral/tufted (M/T) cells. Although it has been previously proposed that the effects of NE are mediated by a direct inhibitory action on granule cells, we have demonstrated that NE could exert it effects through inhibition of excitatory synaptic transmission from M/T cells to granule cells (Trombley and Shepherd, 1992). In order to define further the mechanism underlying NE-mediated inhibition of synaptic transmission, the effects of NE on calcium channel currents were examined using whole-cell recording techniques on bulb neurons in primary culture. NE inhibited high-threshold calcium currents at concentrations that were effective in reducing synaptic transmission. Clonidine, but not isoproterenol, mimicked the effects of NE on calcium currents, suggesting that the effects were mediated through activation of presynaptic alpha-adrenergic receptors. The effects of NE on calcium currents were irreversible in the presence of internal GTP-gamma S and prevented by preincubation with pertussis toxin, results that are consistent with a G-protein-coupled mechanism. Preincubation with pertussis toxin also prevented the effects of NE on synaptic transmission, suggesting that a similar G-protein couple mechanism mediates both effects. Intracellular dialysis with staurosporin or calcium buffering with EGTA did not prevent the effects of NE, suggesting that neither protein phosphorylation nor elevated intracellular calcium were required. These results suggest that NE may inhibit synaptic transmission in the olfactory bulb by reducing calcium currents via a G-protein-coupled alpha-adrenergic receptor.
Trombley
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Section of Neurobiology, Yale University Medical School, New Haven, Connecticut 06510.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology*; D037342:Pertussis Toxin; D013569:Synapses / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium; D009638:Norepinephrine