| Abstrakt: |
The mechanism of quinidine action on rabbit cardiac and skeletal muscle was examined with 'functionally skinned' muscle-fiber preparations. By using these preparations we could correlate measurements of muscle tension with the effect of quinidine on the Ca activation of the contractile proteins and on the Ca uptake and release from the sarcoplasmic reticulum (SR). Effect of quinidine on the contractile proteins. Quinidine concentrations above 0.5 mmol/l increased the maximal Ca-activated tension development 12% for papillary muscle and 5% for soleus (slow-twitch). Adductor magnus (fast-twitch) showed no significant change. Quinidine (0.1-1.0 mmol/l) also increased the submaximal Ca-activated tension development for the three muscle types (papillary muscle=soleus>adductor magnus) and shifted the [Ca]-tension curves to the left in a dose-dependent fashion. Effects of quinidine on the Ca uptake and release from the SR. Sarcoplasmic reticulum of skinned fibers was loaded with Ca (uptake phase), then Ca was released by 25 mmol/l caffeine (release phase) giving a tension transient. The area under the tension transient was used to estimate the amount of Ca released. Quinidine (>0.5 mmol/l) decreased the Ca uptake (soleus>adductor magnus>papillary muscle) and increased the Ca release [papillary muscle=soleus ≫ adductor magnus (only at 1.5 mmol/l, the highest concentration tested)] from the SR of all three muscles in a dose-dependent manner. Quinidine at low concentration (0.1 and 0.5 mmol/l) increased the caffeine-induced tension transient of papillary muscle and higher quinidine concentrations (1.0 and 1.5 mmol/l) decreased the caffeine-induced tension transient of soleus and adductor magnus during both the uptake and release phases. The decreased Ca uptake of papillary muscle in 1.5 mmol/l quinidine was antagonized by increasing the free Mg from 0.032 to 0.32 mmol/l. In summary, quinidine has similar mechanisms of action in all three muscles: increased Ca activation of the contractile proteins, decreased Ca uptake and increased Ca release from the SR in 'functionally skinned' muscle fibers. We conclude that quinidine-induced decreases in Ca uptake by the SR could be responsible for quinidine-induced myocardial depression and that quinidine-induced increases in Ca activation of the contractile proteins and Ca release from the SR could be responsible for the increases in skeletal muscle contraction caused by quinidine. [ABSTRACT FROM AUTHOR] |
Full text from SpringerLink