Inhibition of muscle carbonic anhydrase increases rise and relaxation times of twitches in rat skeletal muscle fibres

Abstract.

Muscle carbonic anhydrase (CA) was inhibited in fibre bundles of the extensor digitorum longus (EDL) and soleus (SOL) muscles from rats. Isometric single twitches were recorded in the absence or presence of the CA inhibitors. The highly membrane-permeable inhibitors L-645,151, chlorzolamide (CLZ) and ethoxzolamide (ETZ) prolonged significantly the values of time-to-peak (ttp) by 5–40 ms (10–40%) in both muscles and the values of the 75% decay time (t_75%) by 30–400 ms (13–110%) in SOL and by 9–17 ms (15–30%) in EDL and increased peak force by 20–55% in SOL and EDL. The poorly membrane-permeable inhibitors benzolamide (BZ) and acetazolamide (ACTZ) had no effects on single twitches. In CO₂-free solution, the effects of L-645,151 on ttp, t_75% and peak force of SOL were reduced drastically. Removal of CO₂ prolonged ttp and t_75%. In skinned fibres, ETZ and CLZ did not increase force production. Intracellular pH (pH_i) in SOL and EDL fibres was not affected by 30–60 min exposure to CLZ, ETZ or BZ. The results of L-645,151, CLZ and ETZ on ttp, t_75% and peak force of twitches are consistent with our hypothesis on the role of the sarcoplasmic reticulum (SR) CA. The SR-CA may mediate sufficiently fast buffering and production of H⁺ in the SR that is exchanged for Ca²⁺ across the SR membrane. We propose that a H⁺ buffering and delivery impaired by CA inhibition slows the kinetics of Ca²⁺ release and reuptake and, as a result, slows twitch ttp and t_75%. Aspects of this hypothesis await further validation.