Differential modulation of caffeine- and IP3-induced calcium release in cultured arterial tissue

To investigate the Ca2+-dependent plasticity of sarcoplasmic reticulum (SR) function in vascular smooth muscle, transient responses to agents releasin g intracellular Ca2+ by either ryanodine (caffeine) or D-myo-inositol 1,4,5 -trisphosphate [IP3; produced in response to norepinephrine (NE), 5-hydroxy tryptamine (5-HT), arginine vasopressin (AVP)] receptors in rat tail arteri al rings were evaluated after 4 days of organ culture. Force transients ind uced by all agents were increased compared with those induced in fresh ring s. Stimulation by 10% FCS during culture further potentiated the force and Ca2+ responses to caffeine (20 mM) but not to NE (10 mu M), 5-HT (10 mu M), or AVP (0.1 mu M) The effect was persistent, and SR capacity was not alter ed after reversible depletion of stores with cyclopiazonic acid. The effect s of serum could be mimicked by culture in depolarizing medium (30 mM K+) a nd blocked by the addition of verapamil (1 mu M) or EGTA (1 mM) to the medi um, lowering intracellular Ca2+ concentration ([Ca2+](i)) during culture. T hese results show that modulation of SR function can occur in vitro by a me chanism dependent on long-term levels of basal [Ca2+](i) and involving ryan odine- but not IP3 receptor-mediated Ca2+ release.