Inhibitory synaptic potentials recorded from mammalian neurones prolonged by blockade of noradrenaline uptake.

1. Intracellular recordings of membrane potential and membrane current were made from neurones of the rat nucleus locus coeruleus and the guinea-pig submucous plexus. These neurones exhibit inhibitory post-synaptic potentials (i.p.s.p.s) which result from noradrenaline acting on alpha 2-adrenoceptors to cause an increase in potassium conductance. 2. Cocaine (0.2-30 microM) reversibly increased the duration of the i.p.s.p. or inhibitory post-synaptic current (i.p.s.c.) in locus coeruleus neurones and submucous plexus neurones by approximately 750% and 350% respectively. The concentrations of cocaine causing half-maximal prolongation of the synaptic current were 3 microM in locus coeruleus and 0.5 microM in submucous plexus. The prolongation was due entirely to a slower rate of decay of the synaptic response. 3. Cocaine (10 microM) produced a maintained hyperpolarization (2-10 mV) or outward current (20-120 pA) in locus coeruleus neurones; in submucous plexus neurones cocaine increased the amplitude and duration of spontaneous i.p.s.p.s. 4. Outward currents produced by superfusion with noradrenaline were increased by cocaine with maximum effects being observed at 10-30 microM-cocaine. The maximum leftward shift in the relation between outward current or membrane hyperpolarization and noradrenaline concentration was 18- to 100-fold in locus coeruleus neurones and 4-fold in submucous plexus neurones. The concentrations of cocaine which caused a half-maximal increase in sensitivity to superfused noradrenaline were similar in both tissues, being 4 microM in locus coeruleus and 2 microM in submucous plexus. 5. These results show that neuronal uptake of noradrenaline released from adrenergic nerves plays a significant role in determining the time course of synaptic potentials mediated by noradrenaline.