Contractile effects of 4-aminopyridine on isolated frog rectus abdominis muscles

Abstract

The contractile effects of 4-aminopyridine (4-AP) on isolated frog rectus abdominis muscles were examined, and compared with KCl-induced contractures. 4-AP (1 – 40 mM) caused slowly developing, concentration-dependent contractures which were not modified by (+)-tubocurarine (2.7 – 13.3 μM). The contractures were prolonged and very slowly relaxed (>30 min) on washout. KCl-induced contractures developed more rapidly and relaxation was equally rapid, both occurring within 90 s of application and washout, respectively. KCl contractures were slightly but significantly (P < 0.05) attenuated by (+)-tubocurarine in concentrations that blocked carbachol contractures. In calcium-free Ringer's solution, KCl (10–120 mM) responses were completely abolished, but 4-AP concentration–response curves were shifted to the right three- to four-fold. The results show that 4-AP causes contracture of the frog rectus abdominis. It is suggested that at the lower concentration employed (<10 mM), 4-AP increases extracellular calcium entry into the muscle, while larger concentrations produce contractures by a direct intracellular mechanism. 4-AP contractures were independent of postjunctional nicotinic cholinoceptor activation.