Norepinephrine modulates excitability of neonatal rat optic nerves through calcium-mediated mechanisms.
We report that norepinephrine markedly increases excitability of neonatal rat optic nerves. To investigate the mechanisms of the norepinephrine-induced excitability increase, we studied isolated optic nerves from 42 neonatal (< three days old) and five adult (> three months old) Long-Evan's hooded rats. Norepinephrine (10(-6), 10(-5) and 10(-4) M) rapidly and reversibly increased the amplitude (mean +/- S.D.: 3.5 +/- 1.7%, 12.1 +/- 2.8% and 35.6 +/- 8.4%) of compound action potentials elicited by submaximal stimulation of neonatal optic nerves. The beta-1 adrenoceptor antagonist atenolol (10(-5) M) blocked the norepinephrine-induced increase in excitability but the alpha antagonist phentolamine (10(-5) M) did not. The beta agonist isoproterenol (10(-5) and 10(-4) M) increased response amplitudes (8.7 +/- 4.1% and 25.8 +/- 4.6%) but the alpha-1 agonist methoxamine and alpha-2 agonist clonidine did not. The beta antagonist propranolol blocked the isoproterenol effect. Replacing Ca2+ with Mg2+ or adding 0.8 mM of Cd2+ reversibly blocked the norepinephrine effects. Extracellular K+ concentrations did not change in optic nerves during norepinephrine application. Blockade of K+ channels with apamin (10(-6) M) or tetraethylammonium (10(-3) M) did not prevent the excitatory effects of norepinephrine. Adult rat optic nerves were insensitive to both norepinephrine (10(-4) M) and isoproterenol (10(-4) M). Our results indicate that norepinephrine increases neonatal optic axonal excitability through Ca(2+)-dependent mechanisms. The data suggest that the adrenoceptors are situated on the axons, that the excitability changes are not due to changes in extracellular K+ concentration or K+ channels sensitive to apamin or tetraethylammonium. The sensitivity of rat optic nerves to norepinephrine declined with age. Axonal adrenoceptors may play a role in optic axonal development and injury.
Honmou
O
O
Department of Neurosurgery, New York University Medical Center, NY 10016, USA.
Young
W
W
D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D009900:Optic Nerve / Q000187:drug effects*; D051381:Rats
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D002104:Cadmium; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine