It is believed that a functionally significant intracellular Ca²⁺ store is absent in frog ventricle and that they depend on extracellular Ca²⁺ for contraction [1]. A series of findings in our lab has convinced us that there must be a functionally significant Ca²⁺ store in frog ventricle. Based on a previous report, we used 4-aminopyridine (4-AP), on frog ventricular strips [2]. Hearts were isolated from frogs (Rana hexadactyla) which were anesthetized with ether and pithed. 2 mm thick ventricular strips were prepared and mounted in a temperature controlled (25-28 °C) bath perfused with oxygenated solution of the following composition (in mmol L^-1): 117 NaCl, 3 KCl, 1 CaCl₂, 1 MgCl₂, 0.2 NaH₂PO₄, 0.8 Na₂HPO₄, 10 glucose, pH 7.4. Free end of the strip was connected to a force-transducer and force of contraction was recorded on a computer. The strip was paced with field stimulation by silver electrodes at 0.2 Hz. Force of contraction was allowed to stabilize for over 30 minutes. Then the tissue was kept quiescent in a Ca²⁺ free solution (containing 0.2 mmol L^-1 EGTA) with normal Na⁺, low Na⁺ or zero Na⁺ (NaCl replaced with LiCl) for 10 minutes. Addition of 16 mmol L^-1 4-AP to the bath, produced contractures in all three Ca²⁺ free solutions. Effect of 4-AP was reversible. Contractures were significantly larger (P=0.006, n=6, Mann-Whitney U test) in zero Na⁺ solution as compared to normal Na⁺ solution. Effect of 4-AP was independent of K⁺ channel blocking effect, since another K⁺ channel blocker, TEA (16 mmol L^-1 ) was unable to produce contracture. 4-AP was able to produce contractures even in Ca²⁺ free solutions with 10 µmol L^-1 Nifedipine, thereby proving that the contractures are due to Ca²⁺ released from an internal store and not due to extracellular Ca²⁺. In conclusion, 4-AP is able to release Ca²⁺ from an intracellular store in frog ventricle. Contractures were larger on inhibition of Ca²⁺ extrusive mode of Na⁺-Ca²⁺ exchanger (NCX). This shows that NCX is an important Ca²⁺ clearing mechanism in frog ventricle. Effect of 4-AP is independent of K⁺ channel blocking action. 4-AP is known to release Ca²⁺ from endoplasmic reticulum of neurons by activating phospholipase C/InsP₃ pathway [3]. This may not be the cause of contracture as neomycin pre-treatment was unable to prevent contractures. It is also known that there are no InsP₃ receptors in frog ventricular myocardium [1]. Another known effect of 4-AP is sarcoendoplasmic reticulum Ca²⁺-ATPase (SERCA) inhibition [4]. SERCA is present in frog ventricule and hence the cause for contracture could be SERCA inhibition.