Is the capacitative model for calcium entry applicable to vascular smooth muscle

Abstract

This investigative effort is focused on mechanisms involved in Ca2+ regulation in vascular smooth muscle (VSM). The depletion of the inositol 1,4,5-trisphosphate C-a2+ --,Loce- lo-g ryanodine or 2,5-di-(tert-butyl)-I,4benzohydroquinone (BHQ) is thought to activate Ca2+ entry from outside to inside in electrically non-excitable cells. In the current studies, tension and unidirectional 45Ca2+ influx experiments were utilized to determine if depletion of the sarcoplasm- ic reticulum (SR) in VSM, an electrically excitable cell type, is sufficient to activate Ca2+ entry mechanisms. Ryanodine and BHQ, alone or in combination, produced small increases in basal tension in aorta and iliac artery in a normal Ca2+ solution. They also reduced the norepinephrine (NE)-induced phasic response in a Ca2+-free solution in both vessels by depleting the intracellular Ca2+ stores in a time- and concentration-dependent manner. The effects of BHQ and ryanodine on tension appeared to be synergistic. Neither BHQ nor ryanodine altered the sustained response directly attributed to NEinduced Ca2+ entry. The depletion of an intracellular Ca2+ store by BHQ or ryanodine was reflected in a reduced total binding of Ca2+ at La3+ resistant, high and low affinity binding sites. Ryanodine, BHQ and NE all increased 45Ca2+ influx and the effects were not additive. Furthermore, depletion of SR Ca2+ by several different mechanisms (histamine, caffeine or a Ca2+-free solution) increased 45Ca2+ influx in all cases. These results indicate that in VSM: 1) BHQ and ryanodine deplete the NE-sensitive Ca2+ pool; 2) depletion of this pool by either BHQ or ryanodine is sufficient to stimulate Ca2+ entry; 3) depletion of this same pool by other mechanisms, including NE, histamine and caffeine, also leads to an increased Ca2+ entry; 4) the Ca2+ entry pathway activated by SR Ca2+ store depletion and the Ca2+ entry pathway activated by NE may be a shared or common pathway; and 5) the degree of filling of the intracellular Ca2+ store directly influences the rate of Ca2+ influx. In conclusion. the capacitative model appears to be a primary mechanism involved in regulating Ca2+ entry in VSM.