Mechanisms of cytosolic Ca^<2+> oscillations following muscarinic receptor activation in single smooth muscle cells

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The present study was made to elucidate the underlying mechanism of oscillations in cytosolic calcium concentration ([Ca^<2+>]i) following activation of muscarinic receptors in single smooth muscle cells of guinea-pig ileum, in an attempt to provide some insights into functional roles of [Ca^<2+>]i oscillations. Changes in [Ca^<2+>]i were measured directly using a Ca^<2+>-sensitive dye or indirectly by recording [Ca^<2+>]i-dependent ionic currents by the patch clamp technique.1.Muscarinic agonist-induced [Ca^<2+>]i oscillations occur as a result of periodic release of Ca^<2+> from internal Ca^<2+> stores. The same mechanism can be operated to induce [Ca^<2+>]i oscillations after activation of G proteins by GTPgammaS.2.Inositol 1,4,5-trisphosphate (InsP3) functions as a Ca^<2+>-releasing second messenger for generation of muscarinic [Ca^<2+>]i oscillations.3.Ca^<2+>-releasing action of InsP3 is inhibited by a rise of [Ca^<2+>]i to a certain level, and loss of the inhibition with falling [Ca^<2+>]i and with time allows InsP3 to act. This [Ca^<2+>]i-dependent inhibition of InsP3 action may contribute to periodic Ca^<2+> release from the stores during muscarinic receptor activation.4.Ca^<2+> influx across the plasma membrane has a crutial role to play in regulation of the frequency of [Ca^<2+>]i oscillations, and the effect is brought about through a mechanism independent of Ca^<2+> store replenishment. The voltage-gated Ca^<2+> channel and an as yet unidentified channel are both involved in Ca^<2+> entry responsible for modulation of [Ca^<2+>]i oscillations.5.Ca^<2+> stores have a Ca^<2+>-induced Ca^<2+> release mechanism in addition to the Ins-P3 induced Ca^<2+> release mechanism, but the former mechanism may little contribute to the generation of muscarinic [Ca^<2+>]i oscillations.