Effects of acetazolamide on transient K+ currents and action potentials in nodose ganglion neurons of adult rats.
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).
Matsumoto
Shigeji
S
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
Yoshida
Shinki
S
Ikeda
Mizuho
M
Kadoi
Jun
J
Takahashi
Masayuki
M
Tanimoto
Takeshi
T
Kitagawa
Junichi
J
Saiki
Chikako
C
Takeda
Mamoru
M
Shima
Yukio
Y
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
D002257:Carbonic Anhydrase Inhibitors; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D015761:4-Aminopyridine; D000086:Acetazolamide