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 (InsP(3)) was released at intervals, by photolysis of 'caged' InsP(3) within the cell, increases in [Ca2+](i) in many cells, as judged from Ca2+-activated K+-current, were all-or-none; release of InsP(3) before a critical interval had elapsed, which was quite stable for an individual cell, resulted in no response. After Ca2+-induced Ca2+ release had been evoked by depolarization, the InsP(3) response was inhibited. Oscillations in [Ca2+](i) evoked by muscarinic receptor activation were unaffected by Ruthenium Red; during these oscillations exogenous InsP(3) 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 InsP(3) were reduced after caffeine-induced responses and recovery of caffeine-induced Ca2+ release was faster than recovery of InsP(3)-induced Ca2+ release. 4. The results support the idea that InsP(3)-induced Ca2+-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 InsP(3)-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.