title: Effects of acetazolamide on transient K+ currents and action potentials in nodose ganglion neurons of adult rats.
abstract: The aim of the present study was to determine whether acetazolamide (AZ) contributes to the inhibition of the fast inactivating transient K(+) current (I(A) ) in adult rat nodose ganglion (NG) neurons. We have previously shown that pretreatment with either AZ or 4-AP attenuated or blocked the CO(2) -induced inhibition of slowly adapting pulmonary stretch receptors in in vivo experiments. The patch-clamp experiments were performed by using the isolated NG neurons. In addition to this, the RT-PCR of mRNA and the expression of voltage-gated K(+) (Kv) 1.4, Kv 4.1, Kv 4.2, and Kv 4.3 channel proteins from nodose ganglia were examined. We used NG neurons sensitive to the 1 mM AZ application. The application of 1 mM AZ inhibited the I(A) by approximately 27% and the additional application of 4-AP (1 mM) further inhibited I(A) by 48%. The application of 0.1 μM α-dendrotoxin (α-DTX), a slow inactivating transient K(+) current (I(D) ) blocker, inhibited the baseline I(A) by approximately 27%, and the additional application of 1 mM AZ further decreased the I(A) by 51%. In current clamp experiments, AZ application (1 mM) increased the number of action potentials due to the decreased duration of the depolarizing phase of action potentials and/or due to a reduction in the resting membrane potential. Four voltage-gated K(+) channel proteins were present, and most (80-90%) of the four Kv channels immunoreactive neurons showed the co-expression of carbonic anhydrase-II (CA-II) immunoreactivity. These results indicate that the application of AZ causes the reduction in I(A) via the inhibition of four voltage-gated K(+) channel (Kv) proteins without affecting I(D).
authors.affiliation: Department of Physiology, Nippon Dental University, School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan. matsu-s@tky.ndu.ac.jp
authors.forename: Shigeji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Shinki
authors.initials: S
authors.lastname: Yoshida
authors.forename: Mizuho
authors.initials: M
authors.lastname: Ikeda
authors.forename: Jun
authors.initials: J
authors.lastname: Kadoi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanimoto
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitagawa
authors.forename: Chikako
authors.initials: C
authors.lastname: Saiki
authors.forename: Mamoru
authors.initials: M
authors.lastname: Takeda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Shima
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000086:Acetazolamide / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D004347:Drug Interactions; D008297:Male; D009474:Neurons / Q000145:classification / Q000187:drug effects*; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000502:physiology; D021122:Protein Subunits; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D015761:4-Aminopyridine; D000086:Acetazolamide