Influence of phospholipase C on some electrical properties of the skeletal muscle membrane.

1. A study was made of the effects of phospholipase C (PhC) on the resting membrane potential, input resistance, action potential and acetylcholine sensitivity of innervated and chronically denervated single muscle fibres of the rat. 2. In doses higher than 1·5 μg/ml. PhC significantly increased the ionic permeability of the muscle membrane (indicated by a fall in input resistance) and reduced the resting membrane potential of innervated fibres. The ‘fast’ or ‘white’ extensor digitorum longus muscle was the most sensitive and the ‘slow’ or ‘red’ soleus the least sensitive muscle. A similar difference was observed among ‘fast’ and ‘slow’ muscles of the chicken, the posterior latissimus dorsi being far more sensitive than the ‘slow’ anterior latissimus dorsi muscle. Chronically denervated muscles were more resistant to these actions of PhC than innervated ones but even after denervation the ‘fast’ muscles remained more sensitive than the ‘slow’ muscles. 3. The action-potential generating mechanism in the ‘fast’ and ‘slow’ muscle was completely and irreversibly blocked by 1·5 μg/ml. of PhC within 1 hr. Furthermore the innervated and chronically denervated muscles were equally sensitive to this effect of PhC. The enzyme caused a gradual increase in the threshold for excitation, reduction in the rate of rise and the amplitude of the action potential. The input resistance and the resting membrane potential were not reduced by this dose of PhC. 4. Acetylcholine sensitivity of chronically denervated muscles was not affected by PhC in doses that abolished the electrical excitability of the membrane. When PhC reduced the input resistance and the resting membrane potential a decrease was also observed in the response to applied acetylcholine. 5. The results suggest that PhC by acting at the polar heads of membrane phospholipids interferes with the ionic carrier mechanism which generates the action potential. The differences in sensitivity between ‘fast’ and ‘slow’ muscles and between innervated and chronically denervated ones are tentatively explained on the basis of heterologous membrane phospholipids and/or variations in their stereochemical arrangement.