Electrophysiological properties of catecholaminergic neurons in the norepinephrine-deficient mouse.
To determine how norepinephrine affects the basic physiological properties of catecholaminergic neurons, brain slices containing the substantia nigra pars compacta and locus coeruleus were studied with cell-attached and whole-cell recordings in control and dopamine beta-hydroxylase knockout (Dbh -/-) mice that lack norepinephrine. In the cell-attached configuration, the spontaneous firing rate and pattern of locus coeruleus neurons recorded from Dbh -/- mice were the same as the firing rate and pattern recorded from heterozygous littermates (Dbh +/-). During whole-cell recordings, synaptic stimulation produced an alpha-2 receptor-mediated outward current in the locus coeruleus of control mice that was absent in Dbh -/- mice. Normal alpha-2 mediated outward currents were restored in Dbh -/- slices after pre-incubation with norepinephrine. Locus coeruleus neurons also displayed similar changes in holding current in response to bath application of norepinephrine, UK 14304, and methionine-enkephalin. Dopamine neurons recorded in the substantia nigra pars compacta similarly showed no differences between slices harvested from Dbh -/- and control mice. These results indicate that endogenous norepinephrine is not necessary for the expression of catecholaminergic neuron firing properties or responses to direct agonists, but is necessary for auto-inhibition mediated by indirect alpha-2 receptor stimulation.
Paladini
C A
CA
Biology Department, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA. carlos.paladini@utsa.edu
Beckstead
M J
MJ
Weinshenker
D
D
D000200:Action Potentials / Q000235:genetics*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000235:genetics; D000068438:Brimonidine Tartrate; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D004558:Electric Stimulation; D004744:Enkephalin, Methionine / Q000494:pharmacology; D008125:Locus Coeruleus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D009638:Norepinephrine / Q000172:deficiency* / Q000494:pharmacology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics
D000316:Adrenergic alpha-Agonists; D017660:Autoreceptors; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000068438:Brimonidine Tartrate; D004744:Enkephalin, Methionine; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine