The Role of Cytosolic Calcium

The concentration of free calcium ions (Ca ) in the cytosol of ASM is central to the contractile response. The concentration of Ca in the cytosol is determined by the relative activity of processes which deliver Ca to the cytosol and which remove Ca from it. Calcium may be delivered either by influx of extracellular Ca, or by release of Ca stored in intracellular organelles, both processes involving the movement of Ca down an electrochemical gradient from pools of high concentration. Conversely, Ca is removed from the cytosol by energy-requiring pumps and by ion-exchange mechanisms which extrude extracellularly, or which refill the intracellular stores. 

The agonist-induced rise in cytosolic Ca associated with contraction can be measured in cultured ASM loaded with the intracellular Ca -sensitive fluorescent dye Fura-2 (Fig. 9.2). The response is biphasic - an initial sharp rise in cytosolic Ca occurs which peaks within the first minute following exposure to agonist. Cytosolic Ca then fidls reaching a plateau level of elevated Ca which is sustained for the duration of exposure to agonist (Kotlikoff etal., 1987 Panettieri aol, 1989 Senn etal., 1990 Murray and Kotlikoff, 1991 Shieh etal., 1991). 

Contractile tension is maintained during this sustained period of only modest elevation of cytosolic Ca by the accompanying processes involving PKC which increase myofilament sensitivity to Ca . Calcium release from 

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