sodium-cyanate and chlorzolamide

In isolated rat soleus and extensor digitorum longus (EDL) muscles, the effects of carbonic anhydrase inhibitors were studied on oxygen consumption as well as lactate release and accumulation after incubation in inhibitors lasting long enough to produce marked changes in contractile parameters and in the concentrations of energy-rich phosphates. The inhibitors used were chlorzolamide (10(-3) M) and NaCNO (10(-2) M). Compared with control muscles, muscles treated with either of the two inhibitors showed a decrease in force, and an increase in time-to-peak as well as in relaxation time. Lactate content and release in soleus and in EDL were increased by factors of 2-3 with both inhibitors. With both inhibitors, oxygen consumption in the red soleus increased by approximately 27%, whereas in EDL, no significant change could be observed. The increase in aerobic metabolic rate in the red soleus only might indicate that the isozyme CA III, which is present only in this type of muscle, is in some way involved in keeping the oxygen consumption low. The increase in anaerobic metabolic rate occurring in both muscles can possibly be explained by increases in Pi and ADP.

Topics: Animals; Carbonic Anhydrase Inhibitors; Cyanates; Energy Metabolism; Female; Isometric Contraction; Lactates; Lactic Acid; Muscle, Skeletal; Oxygen Consumption; Phosphates; Rats; Thiadiazoles

1. 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 longus (EDL) muscles. 2. The muscles were incubated either in Ringer solutions (95% O2/5% CO2 = control) or in solutions to which one of the inhibitors, 5 X 10(-4) 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-to-peak 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.

Topics: Adenosine Triphosphate; Animals; Carbonic Anhydrase Inhibitors; Cyanates; Hydrogen-Ion Concentration; In Vitro Techniques; Isometric Contraction; Muscle Contraction; Muscles; Phosphates; Phosphocreatine; Rats; Rats, Inbred Strains; Thiadiazoles