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 (IA) in adult rat nodose ganglion (NG) neurons. We have previously shown that pretreatment with either AZ or 4‐AP attenuated or blocked the CO2‐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 IA by approximately 27% and the additional application of 4‐AP (1 mM) further inhibited IA by 48%. The application of 0.1 μM α‐dendrotoxin (α‐DTX), a slow inactivating transient K+ current (ID) blocker, inhibited the baseline IA by approximately 27%, and the additional application of 1 mM AZ further decreased the IA 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 IA via the inhibition of four voltage‐gated K+ channel (Kv) proteins without affecting ID.