4-Aminopyridine can induce release of calcium from the sarcoplasmic reticulum of frog heart

4-Aminopyridine (4-AP), a K(+)-channel blocker, has been associated with cellular Ca2+ movements in various excitable tissues but its interaction with intracellular Ca2+ pools has not been described. Spontaneously beating ventricular strips of frog hearts responded to 4-AP (1.6 x 10(-2) M) by contracture that was susceptible to tolerance development when 4-AP was applied in a repetitive manner after washout periods. Under full mechanical inhibition by Ca(2+)-free Ringer or high-K+ Ringer or a combination of both, 4-AP could still produce contracture, a finding indicating that the source of Ca2+ for such an effect should be intracellular Ca2+ pools, namely the sarcoplasmic reticulum. It was concluded that 4-AP could induce release of Ca2+ from internal stores that might be of importance in its cardiac actions.