EFFECTS OF CAFFEINE ON THE MEMBRANE POTENTIALS, MEMBRANE CURRENTS AND CONTRACTILITY OF THE BULLFROG ATRIUM

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1. Effects of caffeine on the action potentials, membrane currents and contractile responses of the bullfrog atrial muscle were investigated by means of the double glycerol-gap technique.
2. Caffeine, 3, 10, and 50 mM in concentration, caused a potentiation of twitch contraction without producing contracture. The potentiation was larger the higher the concentration. The duration of action potential as well as the relaxation time of contraction was prolonged.
3. Under voltage clamped conditions and constant presence of tetrodotoxin (2.5×10^-7g/ml), 5 mM caffeine produced an augmentation and a rapid onset of the active slow inward current, as well as contractile tension, and decreased the membrane cord resistance.
4. The curve of the voltage-tension relationship was shifted to the left and upward by 5 mM caffeine. Maximum augmentation of tension appeared for depolarizing pulses of 60-80 mV.
5. In a preparation pretreated with 4-fold Ca Ringer solution, 10 mM caffeine induced a contracture which was not abolished by 1 mM La⁺⁺⁺.
6. In the presence of 1 mM La⁺⁺⁺, 10 mM caffeine produced an augmentation of twitch contraction and a transient contracture. Caffeine also augmented a sodium-free contracture under the presence of La⁺⁺⁺.
7. These results are interpreted as indicating that:
a) Caffeine acts on both the surface membrane and the sarcoplasmic reticulum. b) It enhances the inward calcium current augmenting the contraction directly and indirectly through the sarcoplasmic reticulum. c) In normal Ringer solution, the amount of the accumulated calcium is very small but is increased by pretreatment in calcium-rich solution. d) La⁺⁺⁺ inhibits both the inward and outward transmembrane calcium movements.