1. Intracellular Regulation of Ion Channels in Cell Membranes
DEBORAH L. LEWIS, Ph.D. 
Mayo Clinic Proceedings 
Volume 65, Issue 8, Pages (August 1990)
DOI: /S (12)
Copyright © 1990 Mayo Foundation for Medical Education and Research Terms and Conditions

2. Fig. 1
a and b, When a receptor is bound by an agonist (A), guanine nucleotide-binding protein (G protein) associates with the receptor. The G-protein trimer splits into α and βγ subunits when guanine triphosphate (GTP) replaces guanine diphosphate (GDP) on the α subunit (Mg2+ present intracellularly). Some α subunits are myristoylated and are thus shown attached to the membrane by this lipophilic group. The βγ subunits are hydrophobic, c, The α subunit then activates the effector in the case of adenylyl cyclase, βγ may act as an activator in other cases. After hydrolysis of GTP to GDP, α and βγ reassociate, and the cycle ends. GTPase = guanine triphosphatase; Pi = inorganic phosphate.
Mayo Clinic Proceedings  , DOI: ( /S (12) )
Copyright © 1990 Mayo Foundation for Medical Education and Research Terms and Conditions

3. Fig. 2
Diagrams of two second-messenger systems activated through G proteins, α, A model effector (adenylyl cyclase) linked to G proteins. Stimulation of the β-adrenergic receptor results in activation of the Gs protein subunit, turning on of adenylyl cyclase, and generation of cyclic adenosine monophosphate (cAMP). cAMP, in turn, binds the regulatory subunit (R) of protein kinase A (A-kinase) and allows the catalytic subunit (CS) to catalyze the phosphorylation of a target protein (for example, Ca2+ channel). AMP and ATP = adenosine monophosphate and triphosphate; Gi and Gs = inhibitory and stimulatory subunits of the G protein; P = phosphate; PDE = phosphodiesterase, b, Phosphatidylinositol pathway. Binding to receptor (for example, muscarinic receptor) activates a G protein to stimulate the enzyme phospholipase C (PLC). PLC catalyzes the splitting of phosphatidylinositol diphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3). DAG activates protein kinase C (PKC) with a dependence on phosphatidylserine (PS) and Ca2+. PKC can then phosphorylate a target protein, such as an ion channel. IP3 probably acts directly on Ca2+-permeable channels in the endoplasmic reticulum to release Ca2+ into the cytoplasm and perhaps to facilitate translocation of PKC to the membrane. Increasing intracellular Ca2+ concentration initiates a vast number of other events in cells. The enzyme phospholipase A2 (PLA2) may also be linked to receptors through G proteins to produce arachidonic acid (also produced by diacylglycerol lipase [DGL] from DAG). Arachidonic acid is metabolized to leukotrienes, epoxides, and prostaglandins, among other intermediate second messengers shown. GpI = phosphatidylinositol G proteins; HETEs = hydroxyeicosatetraenoic acids; IP4 = inositol tetraphosphate; PX = phospholipids.
Mayo Clinic Proceedings  , DOI: ( /S (12) )
Copyright © 1990 Mayo Foundation for Medical Education and Research Terms and Conditions

4. Fig. 3
Diagram summarizing second-messenger effects onion channels. a, L-type Ca2+ channels. These channels are voltage-activated and modulated by protein kinase A (PKA), protein kinase C (PKC), and perhaps direct actions of G protein subunits, b, Three types of K+ channels. The outward rectifiers, which include delayed rectifiers and Ca2+-activated K+ channels, have the current-voltage relationship shown and are modulated by voltage and phosphorylation. The inward-rectifying K+ channels are also multiply regulated as shown, c, Cation channels. See text for details. ATP = adenosine triphosphate; cGMP = cyclic guanine monophosphate; PKA = protein kinase A; V = voltage. Other abbreviations as in Figure 2.
Mayo Clinic Proceedings  , DOI: ( /S (12) )
Copyright © 1990 Mayo Foundation for Medical Education and Research Terms and Conditions

5. Fig. 4
Diagram depicting regulation of exocytosis by several second-messenger systems. A, Putative fusion protein is shown in lipid vesicle. HETEs = hydroxyeicosatetraenoic acids; LPL = lipoprotein lipase; PKA = protein kinase A; PKC = protein kinase C. B, Capacitance steps observed in a degranulating mast cell stimulated by 5 μM guanosine 5′-O-thiotriphosphate. Each capacitance jump represents the fusion of an individual histamine-containing granule. C = cell capacitance in units of fF (femtofarads); G = cell membrane conductance.
Mayo Clinic Proceedings  , DOI: ( /S (12) )
Copyright © 1990 Mayo Foundation for Medical Education and Research Terms and Conditions