Fig. 8. (A ) Model of Ca2+regulation in SH-SY5Y cells. (B ) Schema of cytoplasmic Ca2+([Ca2+]cyt) transients during single (KCl or carbachol) and sequential stimulation in the absence and presence of volatile anesthetics (VAs). KCl depolarization induces opening of voltage-dependent calcium channel, 1allowing Ca2+entry into the cell, which activates the ryanodine-sensitive Ca2+release channels, 6leading to Ca2+release from caffeine-sensitive stores (Caf store); the released Ca2+acts on the IP3receptor, 5inducing an additional Ca2+release from IP3-sensitive stores (IP3store) and in this way contributes to the [Ca2+]cyttransient (thick solid lines). Carbachol stimulation of muscarinic receptors 7increases the production of IP3, which acts on the IP3receptor 5(dotted line), leading to Ca2+released from the IP3-sensitive store; the released Ca2+acts on the ryanodine-sensitive Ca2+release channels, 6inducing an additional Ca2+release from the Caf store and in this way contributes to the [Ca2+]cyttransient (dashed lines). KCl followed by carbachol: In the presence of VAs the KCl-induced [Ca2+]cyttransient is enhanced, but the carbachol-induced [Ca2+]cyttransient is not significantly affected. Carbachol followed by KCl: In the presence of VA the KCl-induced [Ca2+]cyttransient is markedly enhanced, whereas the carbachol-induced [Ca2+]cyttransient is markedly inhibited. Ca2+is removed from the cytosol by the SERCA, 6the PMCA, 3and the Na+–Ca2+exchanger 2(thin solid lines). Vesicles represent a proposed model for explaining the VA action (see text).