Spontaneous transient outward currents: modulation by nociceptin in murinedentate gyrus granule cells

Spontaneous transient outward currents have been found in peripheral neuron s and smooth muscle cells, but rarely in central neurons. Using a nystatin- perforated patch clamp technique, we succeeded in recording spontaneous tra nsient outward currents in mouse dentate gyrus granule cells. Nociceptin/or phanin FQ increased the amplitude and frequency of transient outward curren ts. We consider modulation of spontaneous transient outward currents to be a new means to regulate cell activity in central neurons, and studied their characteristics and mechanism of augmentation. The whole-cell current-volt age relationship showed outward rectification and the reversal potential wa s close to the equilibrium potential for K+. The frequency of spontaneous t ransient outward currents increased at depolarized potentials. Tetraethylam monium. iberiotoxin and a Ca2+ chelator BAPTA-AM inhibited spontaneous tran sient outward currents. These results suggest the involvement of large-cond uctance Ca2+-activated K+ channels. Single-channel recordings in the inside -out configuration revealed Ca2+-activated K+ channels with a conductance r anging from 82 to 352 pS. The augmenting effect of nociceptin/orphanin FQ w as cancelled by [Phe(1)psi (CH2-NH)Gly(2)]Nociceptin(1-13)NH2. Cd2+ did not affect the transient outward currents or augmentation by nociceptin/orphan in FQ. Whereas nociceptin/orphanin FQ, theophylline and cyclic ADP ribose i nduced transient outward currents with short duration observed under contro l conditions, inositol 1,4,5-trisphosphate induced transient outward curren ts with long duration. in addition to those with short duration. Ryanodine inhibited nociceptin/orphan in FQ from augmenting spontaneous transient out ward currents. Our data suggest that Ca2+ sparks transiently activate large -conductance Ca2+-activated K+ channels to induce transient outward current s. Nociceptin/orphanin FQ probably sensitizes ryanodine receptors and incre ases transient outward currents to reduce cell excitability. (C) 2001 Elsev ier Science B.V. All rights reserved.