REGULATION OF THE CYTOSOLIC CA2-MUSCLE CELLS FROM RAT CEREBRAL-ARTERIES( CONCENTRATION BY CA2+ STORES IN SINGLE SMOOTH)

1. There is no general agreement on the presence or role of Ca2+-induc ed Ca2+ release in smooth muscle. In this paper, Ca2+-induced Ca2+ rel ease has been investigated in rat resistance-sized superior cerebral a rteries to determine its role in regulating the cytosolic Ca2+ concent ration ([Ca2+](i)). 2. Pressurized superior cerebral arteries develope d spontaneous oscillations in diameter. These oscillations were abolis hed by ryanodine (an inhibitor of Ca2+-induced Ca2+ release) and remov al of extracellular Ca2+. This suggests, indirectly, that Ca2+-induced Ca2+ release may regulate [Ca2+](i) in the resistance arteries. 3. To determine if Ca2+-induced Ca2+ release could regulate [Ca2+](i), sing le smooth muscle cells were isolated from the superior cerebral artery , voltage clamped in the whole cell configuration and high temporal re solution [Ca2+](i) measurements made. The relationship between the Ca2 + current (I-Ca) and rise in [Ca2+](i) was examined. 4. Depolarization triggered I-Ca and increased [Ca2+](i). The time course of the measur ed increase in [Ca2+](i) closely followed the increase in [Ca2+](i) ex pected from the time-integrated I-Ca, although about 140-fold more Ca2 + entered the cytosol than appeared as free Ca2+. When the cells were dialysed with ryanodine (30 mu M), the Ca2+ transient evoked by the I- Ca was substantially reduced indicating that Ca2+ influx triggered Ca2 + release from an internal store. 5. Voltage pulses to negative membra ne potentials were more effective in triggering Ca2+ release than puls es to positive potentials suggesting that the Ca2+-induced Ca2+ releas e was voltage dependent. However, the release of Ca2+ from the interna l store triggered by caffeine was voltage independent. These results s uggest that the voltage dependence of Ca2+ release is indirect and pos sibly related to tile plasmalemma unitary Ca2+ current magnitude. 6. T he results establish that Ca2+-induced Ca2+ release contributes to dep olarization-evoked increases in [Ca2+](i) in rat resistance-sized supe rior cerebral arteries over the physiological [Ca2+](i) range (100-200 nM). Compared with more positive membrane potentials the efficacy of Ca2+ in triggering release is high at physiological membrane potential s.