Direct action of 4-aminopyridine on the contractility of a fast-contracting muscle in the cat.

1. The effects of 4-aminopyridine on the contractility of the fast-contracting tibialis anterior and the slow-contracting soleus muscles of cats under chloralose anaesthesia have been studied. 2. 4-Aminopyridine, in doses of 0.5 mg/kg and above, produced a slowly developing increase in the twitch tension of directly stimulated chronically denervated and of indirectly stimulated innervated tibialis anterior muscles, but had little or no effect on twitches of soleus muscles. The effect of innervated tibialis anterior muscles was more pronounced than that on chronically denervated muscles, but it was nevertheless concluded that the whole effect on innervated muscles was the result of a direct action on the muscle fibres. The simultaneously occurring facilitatory action on neuromuscular transmission, which is manifested in the anti-curare action of 4-aminopyridine, had a faster time-course and occurred in both the tibialis anterior and the soleus muscles. 3. 4-Aminopyridine antagonized dantrolene sodium on on the tibialis anterior muscle but not on the soleus muscle. The antagonism could be described as physiological antagonism since it simply reflected the opposing actions on contractility of the two drugs. 4. 4-Aminopyridine was without effect on maximal tetanic tension of either the tibialis anterior or the soleus muscle. 5. It seems clear from the literature that a species difference exists with regard to the ability of 4-aminopyridine to increase muscle contractility. The results described in this paper show that muscle differences within the same species also exist.