Ca2+ inhibition of inositol trisphosphate‐induced Ca2+ release in single smooth muscle cells of guinea‐pig small intestine.

1. Single smooth muscle cells from the longitudinal muscle layer of guinea‐pig small intestine were voltage clamped using patch pipettes in the whole‐cell mode. 2. When D‐myo‐inositol 1,4,5‐trisphosphate (InsP3) was released at intervals, by photolysis of ‘caged’ InsP3 within the cell, increases in [Ca2+]i in many cells, as judged from Ca(2+)‐activated K(+)‐current, were all‐or‐none; release of InsP3 before a critical interval had elapsed, which was quite stable for an individual cell, resulted in no response. After Ca(2+)‐induced Ca2+ release had been evoked by depolarization, the InsP3 response was inhibited. Oscillations in [Ca2+]i evoked by muscarinic receptor activation were unaffected by Ruthenium Red; during these oscillations exogenous InsP3 was not effective close to, or shortly after, peak [Ca2+]i but was effective at other times. 3. Reproducible release of Ca2+ and elevation of [Ca2+]i could be produced by brief (up to 0.5 s) pressure applications of 10 mM caffeine at intervals of 10 s or greater but caffeine itself rarely evoked oscillations in [Ca2+]i. Responses to flash release of InsP3 were reduced after caffeine‐induced responses and recovery of caffeine‐induced Ca2+ release was faster than recovery of InsP3‐induced Ca2+ release. 4. The results support the idea that InsP3‐induced Ca(2+)‐store release can be inhibited by a certain level of [Ca2+]i at a time when Ca2+ stores have refilled and can be released by caffeine; they also support the suggestion that during oscillations of [Ca2+]i evoked by muscarinic receptor activation, Ca2+ inhibition of InsP3‐induced Ca2+ release at some critical level of [Ca2+]i allows Ca2+ stores to refill and leads to a fall in [Ca2+]i so contributing to the oscillations which are observed.