Benzolamide inhibits low-threshold calcium currents in hippocampal pyramidal neurons

1. Benzolamide is a poorly permeant sulfonamide inhibitor of the enzyme carbonic anhydrase. We studied the effect of benzolamide on low-threshold (LT) Ca currents in neonatal hippocampal CA1 neurons. 2. In hippocampal slices, benzolamide (2-10 μM) inhibited the LT current 30-75% in voltage- clamped CA1 pyramidal cells (n = 6). In slices bathed in N-2- hydroxypiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered Ringer, benzolamide also reduced the LT current, indicating that the action of the drug was not bicarbonate dependent. 3. Benzolamide inhibited LT Ca currents 20-75% in acutely dissociated CA1 neurons in HEPES (n = 18): inhibition was 36 ± 8% (mean ± SE; n = 7) and 50 ± 8% (n = 7) at 10 and 50 μM benzolamide, respectively. By contrast, high-threshold calcium currents recorded in CA1 pyramidal cells (n = 18) and dorsal root ganglion neurons (n = 4) were virtually unaffected by benzolamide. 4. These results indicate that benzolamide inhibits LT Ca channels in central neurons and suggest caution in the use of this agent to inhibit extracellular carbonic anhydrase in excitable tissues.