Key Concepts of Section 15.6

• A small rise in cytosolic Ca²⁺ induces a variety of responses in different cells, including hormone secretion, contraction of muscle, and platelet aggregation (see Table 15-4).

• Many hormones bind GPCRs coupled to G proteins containing a G_αo or G_αq subunit. The effector protein activated by GTP-bound G_αo or G_αq is a phospholipase C enzyme.

• Phospholipase C cleaves a phospholipid known as PI(4,5)P₂, generating two second messengers: diffusible IP₃ and membrane-bound DAG (see Figure 15-33).

• IP₃ triggers the opening of IP₃-gated Ca²⁺ channels in the endoplasmic reticulum and elevation of cytosolic free Ca²⁺.

• Opening of IP₃-gated Ca²⁺ channels in the endoplasmic reticulum also leads to an increase in Ca²⁺ in the mitochondrial matrix and an acceleration of ATP synthesis (see Figure 15-35).

• Depletion of ER Ca²⁺ stores leads to the opening of plasma-membrane store-operated Ca²⁺ channels and an influx of Ca²⁺ from the extracellular medium (see Figure 15-34b).

• The Ca²⁺-calmodulin complex regulates the activity of many different proteins, including PDE and protein kinases and phosphatases that control the activity of various transcription factors.

• In response to elevated cytosolic Ca²⁺, protein kinase C is recruited to the plasma membrane, where it is activated by DAG (see Figure 15-34a).

• Glycogen breakdown and synthesis is coordinately regulated by the second messengers Ca²⁺ and cAMP, whose levels are regulated by neural and hormonal stimulation, respectively (see Figure 15-37).

• Stimulation of acetylcholine GPCRs on endothelial cells induces an increase in cytosolic Ca²⁺ and subsequent synthesis of NO. After diffusing into surrounding smooth muscle cells, NO activates an intracellular guanylate cyclase to synthesize cGMP. The resulting increase in cGMP leads to activation of protein kinase G, which triggers a pathway resulting in muscle relaxation and vasodilation (see Figure 15-38).