title: cGMP activates a pH-sensitive leak K+ current in the presumed cholinergic neuron of basal forebrain.
abstract: In an earlier study, we demonstrated that nitric oxide (NO) causes the long-lasting membrane hyperpolarization in the presumed basal forebrain cholinergic (BFC) neurons by cGMP-PKG-dependent activation of leak K+ currents in slice preparations. In the present study, we investigated the ionic mechanisms underlying the long-lasting membrane hyperpolarization with special interest in the pH sensitivity because 8-Br-cGMP-induced K+ current displayed Goldman-Hodgkin-Katz rectification characteristic of TWIK-related acid-sensitive K+ (TASK) channels. When examined with the ramp command pulse depolarizing from -130 to -40 mV, the presumed BFC neurons displayed a pH-sensitive leak K+ current that was larger in response to pH decrease from 8.3 to 7.3 than in response to pH decrease from 7.3 to 6.3. This K+ current was similar to TASK1 current in its pH sensitivity, whereas it was highly sensitive to Ba(2+), unlike TASK1 current. The 8-Br-cGMP-induced K+ currents in the presumed BFC neurons were almost completely inhibited by lowering external pH to 6.3 as well as by bath application of 100 microM Ba(2+), consistent with the nature of the leak K+ current expressed in the presumed BFC neurons. After 8-Br-cGMP application, the K+ current obtained by pH decrease from 7.3 to 6.3 was larger than that obtained by pH decrease from pH 8.3 to 7.3, contrary to the case seen in the control condition. These observations strongly suggest that 8-Br-cGMP activates a pH- and Ba(2+)-sensitive leak K+ current expressed in the presumed BFC neurons by modulating its pH sensitivity.
authors.affiliation: Department of Neuroscience and Oral Physiology, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Toyoda
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.forename: Hajime
authors.initials: H
authors.lastname: Sato
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Dempo
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ohashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hirai
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Maeda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Youngnam
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000818:Animals; D001464:Barium / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000187:drug effects*; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats
chemical_list: D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D001464:Barium; C016276:8-bromocyclic GMP; D006152:Cyclic GMP