Changes of response to caffeine in Ca(2+)-deficient medium in guinea-pig tenia coli

1. After the washing out of the first caffeine, the second 25 mM caffeine-induced tension was about 50% of the first response in tenia coli. Cyclopiazonic acid (CPA), a specific sarcoplasmic reticulum Ca(2+)-ATPase blocker, almost inhibited the contraction to the next application of caffeine after the washing out caffeine in the presence of CPA. The peak tension to caffeine increased after the pretreatment with 10 mM K+ for 1 min. After pretreatment with K+ in the presence of 10(-7) M nifedipine (only phasic response), the tension to caffeine also increased. 2. The response to caffeine was rapidly reduced after incubation in a Ca(2+)-free medium and was abolished after 6 min of incubation. However, the response to caffeine in Ca(2+)-free medium 30 sec. after pretreatment with 10 mM K+ in normal Ca medium was larger. 3. These results suggest that, when the cell membrane is in the resting state, Ca2+ enters the cytoplasm by a leaky pathway and enters storage sites through Ca(2+)-ATPase. Furthermore, when the cell membrane is depolarized for a short period (less than 1 min), Ca2+ entry occurs, leading to refilling of the Ca2+ storage sites utilized by caffeine. The retention of Ca2+ in the storage sites in the Ca(2+)-free condition in tenia coli was less relative to the position in vascular smooth muscle.