kappa-opioid receptor activation inhibits post-spike depolarizing after-potentials in rat supraoptic nucleus neurones in vitro

Endogenous agonists acting at kappa-opioid receptors modulate the discharge activity of hypothalamic supraoptic nucleus vasopressin cells in vivo. Pha sic activity in vasopressin cells is known to depend critically on intrinsi c mechanisms involving post-spike depolarizing after-potentials and we hypo thesized that inhibition of phasic bursting by an endogenous kappa-agonist may result from reducing the magnitude of depolarizing afterpotentials, To investigate this possibility, intracellular sharp electrode recordings were obtained from supraoptic nucleus cells impaled in superfused explants of r at hypothalamus. Bath application of the selective kappa-agonist, U50,488H (0.1-1 mu M), decreased the spontaneous firing rate of magnocellular neuros ecretory cells (by 94.0 +/- 4.5% at 1 mu M, mean +/- SEM; P = 0.02, n = 4). U50,488H did not alter membrane potential (0.9 +/- 0.8 mV hyperpolarizatio n at 1 mu M, P = 0.17, n = 8) or input resistance (11.0 +/- 4.5% increase a t 1 mu M, P = 0.09, n = 5), U50,488H (0.1 and 1 mu M, both n = 5) reduced d epolarizing afterpotential amplitude (by 29.9 +/- 9.3 and 78.0 +/- 0.6%, re spectively, P < 0.001) in eight cells in which the baseline membrane potent ial was kept constant by de-current injection and in which a depolarizing a fter-potential was evoked every 25-40 s by a brief (40-80 ms) train of 3-6 action potentials (the number of spikes in the trains was kept constant for each cell). Thus, kappa-opioid receptor activation reduces depolarizing af ter-potential amplitude in supraoptic nucleus cells and this may underlie t he reduction in burst duration of vasopressin cells caused by an endogenous kappa-agonist in vivo.