Effects of carbonic anhydrase inhibitors on contraction, intracellular pH and energy‐rich phosphates of rat skeletal muscle.

Abstract

SUMMARY1. The effects of carbonic anhydrase inhibitors on contractile parameters, intracellular pH (pHi) and energy-rich phosphates were studied in isolated rat soleus and extensor digitorum longs (EDL) muscles.2. The muscles were incubated either in Ringer solutions (95% 02/5% CO2 = control) or in solutions to which one of the inhibitors, 5 x 10' M-chlorzolamide or 10-2 m-NaCNO, had been added. Muscles were stimulated directly and contracted under isometric conditions.3. Compared with control muscles, both inhibitor-treated muscles showed a significantly decreased tetanic force and an increased half-relaxation time of twitches and tetani. Chlorzolamide increased time-to-peak in both muscles. Cyanate decreased isometric twitch force in both muscles.4. Both inhibitors decreased pHi in both muscles; chlorzolamide by 0.1 unit, cyanate by 0-4 unit in soleus and by 0-8 unit in EDL.5. Chlorzolamide increased the concentrations of creatine and inorganic phosphate (Pi) in soleus (the effect of chlorzolamide was not studied in EDL). Cyanate caused these same changes in soleus as well as EDL and in addition decreased the concentrations of ATP and phosphocreatine in soleus and EDL.6. In muscles acidified by either low external HCO3-(2 mM) or by elevated Pco2(30 % CO2 in the gas phase) in the bath, decreases in isometric force and increases in half-relaxation time of tetani were observed. In addition there were increases in muscle Pi. These effects were more pronounced with 30% CO2 than with 2 mM-HCO3-. 7. Neither acidifying solutions prolonged either half-relaxation time or time-topeak of twitches.8. We conclude that carbonic anhydrase inhibition exerts its effect (a) on isometric tension at least partly via an elevated Pi (perhaps in combination with lowered pHi);(b) on the half-relaxation time of tetani by means of lowered pHi and elevated concentration of Pi; (c) on relaxation and time-to-peak of twitches by some unknown mechanism, neither directly by a change in pHi nor in Pi.MS 7639

Interplay between a cytosolic and a cell surface carbonic anhydrase in pH homeostasis and acid tolerance of Leishmania

“…Although the maximum growth defect was observed in the LmCA1 +/− mutant strains was lowered by about 0.2, 0.1 and 0.3 pH units, respectively, as compared to the wild type. This finding is consistent with the role of carbonic anhydrases in cytosolic buffering that are seen in various cell types across species (Thomas, 1976;Geers and Gros, 1990;Leniger et al, 2004;Marcus et al, 2005;Schewe et al, 2008). In fact, a similar drop in intracellular pH has been observed by us previously when carbonic anhydrase activity in L. major was pharmacologically inhibited with metal dithiocarbamates (Pal et al, 2015).…”

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

“…First, because of the short diffusion distances in the fibre bundles, no limitation of O 2 supply is expected. Second, as seen here, CA inhibitors exert their effects in this preparation within 1-3 min instead of 6 h as in whole muscles [9,10]. Third, as shown below, inhibitory effects on twitches are reversible, which is not the case with isolated whole muscles.…”

“…For this purpose, the SR-CA was inhibited by different sulfonamides, which are specific CA inhibitors, and the impact of the inhibition of the enzyme on isometric single twitches was tested using small fibre bundles of the extensor digitorum longus (EDL) and the soleus (SOL) from rats. These muscle bundles consist of about 20-30 muscle cells and have several advantages compared with isolated whole-muscle preparations as used in other studies [9,10,12]. First, because of the short diffusion distances in the fibre bundles, no limitation of O 2 supply is expected.…”

Extramitochondrial domain rich in carbonic anhydrase activity improves myocardial energetics

“…4F), suggesting a role for CA activity in improving cardiac energetics. Interestingly, reduced energetics have been reported in skeletal muscle treated with CA inhibitors (57) or from CAIII-knockout animals (58). At constant pH i , a down-stream effect of a decreased PCr/ATP ratio is reduced cardiac contractility (45).…”