NOREPINEPHRINE MODULATES EXCITABILITY OF NEONATAL RAT OPTIC NERVES THROUGH CALCIUM-MEDIATED MECHANISMS

We report that norepinephrine markedly increases excitability of neona tal rat optic nerves. To investigate the mechanisms of the norepinephr ine-induced excitability increase, we studied isolated optic nerves fr om 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 amplitudes (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 norepinephr ine-induced increase in excitability but the alpha antagonist phentola mine (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 c hange 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 isoprot erenol (10(-4) M). Our results indicate that norepinephrine increases neonatal optic axonal excitability through Ca2+-dependent mechanisms. The data suggest that the adrenoceptors are situated on the axons, tha t the excitability changes are not due to changes in extracellular Kconcentration 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.