SUSTAINED CONTRACTION PRODUCED BY CAFFEINE AFTER RYANODINE TREATMENT IN THE CIRCULAR MUSCLE OF THE GUINEA-PIG GASTRIC ANTRUM AND RABBIT PORTAL-VEIN

1 Caffeine inhibited spontaneous mechanical activity at 0.3-1 mM, but produced a tonic contraction at concentrations higher than 3 mM in the circular muscle of the guinea-pig gastric antrum. In the circular mus cle of the rabbit portal vein, caffeine at concentrations higher than 1 mM produced an early phasic contraction followed by a small tonic co mponent. The caffeine-induced contraction was abolished by removal of the external Ca2+ more rapidly in the gastric antrum than the portal v ein. 2 When the preparations were pretreated with ryanodine (1 mu M) a sustained contraction developed on wash-out of caffeine (10 mM) both in the gastric antrum and portal vein. This contraction was not affect ed by nicardipine (3 mu M) or verapamil (3 mu M), but was readily abol ished by removal of the external Ca2+ or by addition of cobalt (1 mM). Spontaneous electrical activity, the slow wave, in gastric muscles wa s blocked in the presence of 10 mM caffeine, but reappeared during the sustained contraction. 3 Both the contractions induced directly by ca ffeine and those produced following caffeine wash-out after ryanodine treatment were accompanied by a maintained increase in intracellular C a2+ concentration measured with fura-2. 4 The presence or absence of C a2+ during the application of ryanodine did not affect the ability of caffeine to initiate sustained contractions, provided Ca2+ was present during the exposure to caffeine. 5 It is concluded that caffeine can induce a sustained contraction after ryanodine treatment both in the g uinea-pig gastric antrum and rabbit portal vein, by activating a Ca2influx pathway insensitive to organic Ca2+ channel blockers. No clear evidence was obtained for involvement of the Ca2+ influx pathway activ ated through depletion of intracellular Ca2+ stores. A hypothesis is p roposed that the plasma membrane of these preparations is similar to t he sarcoplasmic reticulum membrane in that Ca2+ permeability can be in creased almost irreversibly by a combination of caffeine and ryanodine in the presence of the external Ca2+.