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

• Published in: Brain research 2001-11, Vol.917 (2), p.191-205
• Main Authors: Shirasaki, Tetsuya, Houtani, Takeshi, Sugimoto, Tetsuo, Matsuda, Hiroko
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Ca 2+ spark; Calcium - physiology; Central nervous system; Cyclic ADP ribose; Dentate Gyrus - cytology; Dentate Gyrus - drug effects; Dentate Gyrus - physiology; Electric Conductivity; Electrophysiology; Fundamental and applied biological sciences. Psychology; Inositol 1,4,5-trisphosphate; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Nociceptin; Opioid Peptides - pharmacology; Orphanin FQ; Potassium Channels - physiology; STOCs; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02916-X

Spontaneous transient outward currents have been found in peripheral neurons and smooth muscle cells, but rarely in central neurons. Using a nystatin-perforated patch clamp technique, we succeeded in recording spontaneous transient outward currents in mouse dentate gyrus granule cells. Nociceptin/orphanin FQ increased the amplitude and frequency of transient outward currents. 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–voltage relationship showed outward rectification and the reversal potential was close to the equilibrium potential for K +. The frequency of spontaneous transient outward currents increased at depolarized potentials. Tetraethylammonium, iberiotoxin and a Ca 2+ chelator BAPTA-AM inhibited spontaneous transient outward currents. These results suggest the involvement of large-conductance Ca 2+-activated K + channels. Single-channel recordings in the inside-out configuration revealed Ca 2+-activated K + channels with a conductance ranging from 82 to 352 pS. The augmenting effect of nociceptin/orphanin FQ was cancelled by [Phe 1ψ(CH 2-NH)Gly 2]Nociceptin(1–13)NH 2. Cd 2+ did not affect the transient outward currents or augmentation by nociceptin/orphanin FQ. Whereas nociceptin/orphanin FQ, theophylline and cyclic ADP ribose induced transient outward currents with short duration observed under control conditions, inositol 1,4,5-trisphosphate induced transient outward currents with long duration, in addition to those with short duration. Ryanodine inhibited nociceptin/orphanin FQ from augmenting spontaneous transient outward currents. Our data suggest that Ca 2+ sparks transiently activate large-conductance Ca 2+-activated K + channels to induce transient outward currents. Nociceptin/orphanin FQ probably sensitizes ryanodine receptors and increases transient outward currents to reduce cell excitability.