GTP-binding Proteins Mediate Transmitter Inhibition of Voltage-dependent Calcium Channels

Overview

Journal Nature

Specialty Science

Date 1986 Feb 20

PMID 2419757

Citations 146

Authors

G G Holz 4th

S G Rane

K Dunlap

Affiliations

Soon will be listed here.

Abstract

The modulation of voltage-dependent calcium channels by hormones and neurotransmitters has important implications for the control of many Ca2+-dependent cellular functions including exocytosis and contractility. We made use of electrophysiological techniques, including whole-cell patch-clamp recordings from dorsal root ganglion (DRG) neurones, to demonstrate a role for GTP-binding proteins (G-proteins) as signal transducers in the noradrenaline- and gamma-aminobutyric acid (GABA)-induced inhibition of voltage-dependent calcium channels. This action of the transmitters was blocked by: (1) preincubation of the cells with pertussis toxin (a bacterial exotoxin catalysing ADP-ribosylation of G-proteins); or (2) intracellular administration of guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S), a non-hydrolysable analogue of GDP that competitively inhibits the binding of GTP to G-proteins. Our findings provide the first direct demonstration of the G-protein-mediated inhibition of voltage-dependent calcium channels by neurotransmitters. This mode of transmitter action may explain the ability of noradrenaline and GABA to presynaptically inhibit Ca2+-dependent neurosecretion from DRG sensory neurones.

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References

Reuter H, Scholz H . The regulation of the calcium conductance of cardiac muscle by adrenaline. J Physiol. 1977; 264(1):49-62. PMC: 1307747. DOI: 10.1113/jphysiol.1977.sp011657. View

Dichter M, Fischbach G . The action potential of chick dorsal root ganglion neurones maintained in cell culture. J Physiol. 1977; 267(2):281-98. PMC: 1283615. DOI: 10.1113/jphysiol.1977.sp011813. View

Dunlap K, Fischbach G . Neurotransmitters decrease the calcium ocmponent of sensory neurone action potentials. Nature. 1978; 276(5690):837-9. DOI: 10.1038/276837a0. View

Sabol S, Nirenberg M . Regulation of adenylate cyclase of neuroblastoma x glioma hybrid cells by alpha-adrenergic receptors. I. Inhibition of adenylate cyclase mediated by alpha receptors. J Biol Chem. 1979; 254(6):1913-20. View

Eckstein F, Cassel D, Levkovitz H, Lowe M, SELINGER Z . Guanosine 5'-O-(2-thiodiphosphate). An inhibitor of adenylate cyclase stimulation by guanine nucleotides and fluoride ions. J Biol Chem. 1979; 254(19):9829-34. View

Cassel D, Eckstein F, Lowe M, SELINGER Z . Determination of the turn-off reaction for the hormone-activated adenylate cyclase. J Biol Chem. 1979; 254(19):9835-8. View

Kupfermann I . Modulatory actions of neurotransmitters. Annu Rev Neurosci. 1979; 2:447-65. DOI: 10.1146/annurev.ne.02.030179.002311. View

Hazeki O, Ui M . Modification by islet-activating protein of receptor-mediated regulation of cyclic AMP accumulation in isolated rat heart cells. J Biol Chem. 1981; 256(6):2856-62. View

Shain W, Carpenter D . Mechanisms of synaptic modulation. Int Rev Neurobiol. 1981; 22:205-50. DOI: 10.1016/s0074-7742(08)60294-9. View

10.

Hamill O, Marty A, Neher E, Sakmann B, Sigworth F . Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981; 391(2):85-100. DOI: 10.1007/BF00656997. View

11.

Dunlap K . Two types of gamma-aminobutyric acid receptor on embryonic sensory neurones. Br J Pharmacol. 1981; 74(3):579-85. PMC: 2071768. DOI: 10.1111/j.1476-5381.1981.tb10467.x. View

12.

Dunlap K, Fischbach G . Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones. J Physiol. 1981; 317:519-35. PMC: 1246805. DOI: 10.1113/jphysiol.1981.sp013841. View

13.

Jakobs K . Determination of the turn-off reaction for the epinephrine-inhibited human platelet adenylate cyclase. Eur J Biochem. 1983; 132(1):125-30. DOI: 10.1111/j.1432-1033.1983.tb07336.x. View

14.

GILMAN A . G proteins and dual control of adenylate cyclase. Cell. 1984; 36(3):577-9. DOI: 10.1016/0092-8674(84)90336-2. View

15.

Katada T, Bokoch G, Northup J, Ui M, GILMAN A . The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Properties and function of the purified protein. J Biol Chem. 1984; 259(6):3568-77. View

16.

Wojcik W, Neff N . gamma-aminobutyric acid B receptors are negatively coupled to adenylate cyclase in brain, and in the cerebellum these receptors may be associated with granule cells. Mol Pharmacol. 1984; 25(1):24-8. View

17.

Lemos J, Levitan I . Intracellular injection of guanyl nucleotides alters the serotonin-induced increase in potassium conductance in Aplysia neuron R15. J Gen Physiol. 1984; 83(2):269-85. PMC: 2215624. DOI: 10.1085/jgp.83.2.269. View

18.

NISHIZUKA Y . The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984; 308(5961):693-8. DOI: 10.1038/308693a0. View

19.

Jakobs K, Aktories K, Schultz G . Mechanisms and components involved in adenylate cyclase inhibition by hormones. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1984; 17:135-43. View

20.

Canfield D, Dunlap K . Pharmacological characterization of amine receptors on embryonic chick sensory neurones. Br J Pharmacol. 1984; 82(3):557-65. PMC: 1987005. DOI: 10.1111/j.1476-5381.1984.tb10794.x. View