The Effect of Caffeine on Radiocalcium Movement in Frog Sartorius

Abstract

Caffeine increases resting calcium influx approximately threefold in normally polarized and in potassium-depolarized fibers of frog sartorius muscles. It does not affect the transient rapid increase in calcium influx that occurs at the beginning of a potassium depolarization. Calcium outflux in Ringer's solution, in zero calcium Ringer's solution, and in zero calcium Ringer's solution plus 0.004 M EDTA is also markedly increased by caffeine. The increased out-flux reaches a rate which is approximately the same as the increased calcium influx. One interpretation of the findings is that caffeine reduces the binding of calcium both in the membrane and in the myoplasm; this increases the "permeability" to calcium and the ionic activity of calcium in muscle. This interpretation is consistent with the view that the contractile state of muscle is dependent at least in part on the thermodynamic activity of calcium in the muscle fibers.Experiments by Axelsson and Thesleff (I) suggested that the alkaloid caffeine (free base) initiates a process in the muscle which leads to contraction, and that this process is not mediated by changes in resting potential or in ionic permeability of the muscle membrane. The addition of Ca up to five times its normal concentration or the depletion of Ca by soaking the muscle in 0.1 per cent ethylenediaminetetraacetic acid (EDTA) has no observable effect on the contracture produced by caffeine. Calcium has been suggested as a possible link between depolarization and contraction (6, 9, 13, 3), a suggestion supported by recent findings (2, 15). The following experiments were performed to determine whether caffeine might still be exerting its effects by way of the calcium in the muscle, especially that remaining after E D T A treatment (5).

Facilitation of frog neuromuscular transmission by sodium fluoride

“…Most laboratories doing similar experiments use theophylline (a xanthine derivative) on the assumption that observed effects are due to inhibition of phosphodiesterase, even though theophylline has other actions (Standaert & Dretchen, 1981) e.g., induction of the calcium release from its storage site in the cytoplasm (Bianchi, 1961). To deal with the possibility that another action might be responsible for the increase in the transmitter release, we used papaverine (a non-xanthine derivative), which shares theophylline's capacity to inhibit phosphodiesterase but not its other characteristics (Standaert & Dretchen, 1981).…”

Effects of calcium and guanosine‐3',5'‐cyclic‐monophosphoric acid on receptor potentials of toad rods.

“…There are two main problems which may complicate the interpretation of data resulting from the manipulation of Ca2+ or cGMP. First, the procedures used to change the internal concentration of Ca2+ and cGMP may affect other cell functions (Bianchi, 1961;Sheppard, 1970;Plagemann, 1974;Gaska, Canter & Shelanski, 1975;Klausner, Bhalla, Dragsten, Hoover & Karnovsky, 1980). A second problem is that cGMP and Ca2+ may play interacting roles in rod physiology since changes in the concentration ofone change the concentration ofthe other (Cohen et al 1978;Kilbride & Ebrey, 1979;Kilbride, 1980;Polans et al 1981).…”

Effects of sulphydryl inhibitors on frog sartorius muscle: N‐ethylmaleimide

“…The kinetics of rigour development by NEM and its effect on 45Ca efflux were similar, suggesting a relationship between the two effects. In these experiments, NEM was added to the muscle bath during a period of time when "5Ca is assumed to be emerging primarily from the sarcoplasmic reticulum (Bianchi, 1961 ;Isaacson & Sandow, 1967). If this assumption is valid, then a sustained increase in 45Ca efflux from the muscle reflects an increase in the amount of free intracellular calcium released from the sarcoplasmic reticulum.…”