A CAFFEINE INDEPENDENT CA-2+ INDUCED CA-2+ RELEASE MECHANISM IN CULTURED HUMAN VASCULAR SMOOTH-MUSCLE CELLS

Oscillations in intracellular calcium ([Ca2+]i) can be evoked in intact cultured human vascular smooth muscle cells. In nominally Ca2+ free media the oscillations persist, although with a progressive decrease in amplitude and frequency, suggesting the cyclical mobilisation of Ca2+ from internal stores. Kinetic analysis of repeated brief pulses of agonist, in nominally Ca2+ free solution, suggests the presence of at least two release processes. Obvious candidates are the IP3 induced Ca2+ release (IICR) system and the Ca2+ induced Ca2+ release (CICR) system. Caffeine, which can activate CICR in many cell types, has no Ca2+ mobilising action suggesting the possible absence of CICR. In fact caffeine produces a potent inhibition of IICR. The thiol reagent thimerosal can activate regenerative releases of Ca2+ from an internal store. This appears to be different from the IICR store although a sensitising action of thimerosal on the IICR mechanism can be demonstrated. If an independent CICR mechanism exists in these cultured human smooth muscle cells then it must be of a different type to those described in cardiac and skeletal muscle.