Search PubMedSearch

PubMed · 6296856

cAMP-mediated decrease in K+ conductance evoked by serotonin and dopamine in the same neuron: a biochemical and physiological single-cell study.

Abstract

The extracellular application of either serotonin or dopamine and the intracellular injection of cAMP all evoke in the same identified neurons of the snail Helix aspersa inward currents associated with a decrease in K+ conductance. The serotonin-, dopamine-, and cAMP-induced inward currents all show the same maximal amplitude. When the response to one transmitter is maximal, the response to the other is blocked. Using a single-cell microassay, we found that both serotonin and dopamine stimulate the adenylate cyclase [adenosine triphosphate pyrophosphate-lyase (cyclizing), EC 4.6.6.1] activity of the neurons giving the inward-current responses; on the other hand, the adenylate cyclase activity of a neuron that does not show the serotonin- and dopamine-induced currents was not stimulated by the transmitters. In contrast with the nonsummation of the maximal inward-current responses, the maximal stimulating effects of the transmitters on the enzyme activity are additive. The diterpene forskolin, which stimulates the adenylate cyclase activity of the single cells 9-fold, also evokes an inward current. We conclude that single snail neurons are endowed with independent serotonin and dopamine receptors linked to the adenylate cyclase. Activation of each of these receptors evokes a cAMP-mediated decrease in K+ conductance. The physiological interaction between the transmitters probably takes place at a late step in the chain of events leading from the increase in cAMP to the closing of the K+ channels.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

P Deterre, D Paupardin-Tritsch, J Bockaert, H M Gerschenfeld. 1982. cAMP-mediated decrease in K+ conductance evoked by serotonin and dopamine in the same neuron: a biochemical and physiological single-cell study.. https://doi.org/10.1073/pnas.79.24.7934

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse.

Rapid expansion of available data, both phenotypic and genotypic, for multiple strains of mice has enabled the development of new methods to interrogate the mouse genome for functional genetic perturbations. In silico mapping provides an expedient way to associate the natural diversity of phenotypic traits with ancestrally inherited polymorphisms for the purpose of dissecting genetic traits. In mouse, the current single nucleotide polymorphism (SNP) data have lacked the density across the genome and coverage of enough strains to properly achieve this goal. To remedy this, 470,407 allele calls were produced for 10,990 evenly spaced SNP loci across 48 inbred mouse strains. Use of the SNP set with statistical models that considered unique patterns within blocks of three SNPs as an inferred haplotype could successfully map known single gene traits and a cloned quantitative trait gene. Application of this method to high-density lipoprotein and gallstone phenotypes reproduced previously characterized quantitative trait loci (QTL). The inferred haplotype data also facilitates the refinement of QTL regions such that candidate genes can be more easily identified and characterized as shown for adenylate cyclase 7.

Adenylyl Cyclases

Sites important for PLCbeta2 activation by the G protein betagamma subunit map to the sides of the beta propeller structure.

The betagamma subunits of the heterotrimeric GTP-binding proteins (G proteins) that couple heptahelical, plasma membrane-bound receptors to intracellular effector enzymes or ion channels directly regulate several types of effectors, including phospholipase Cbeta and adenylyl cyclase. The beta subunit is made up of two structurally different regions: an N-terminal alpha helix followed by a toroidal structure made up of 7 blades, each of which is a twisted beta sheet composed of four anti-parallel beta strands (Wall, M. A., Coleman, D. E., Lee, E., Iñiguez-Lluhi, J. A., Posner, B. A., Gilman, A. G., and Sprang, S. R. (1995) Cell 83, 1047-1058; Lambright, D. G., Sondek, J., Bohm, A., Skiba, N. P., Hamm, H. E., and Sigler, P. B. (1996) Nature 379, 311-319). We have previously shown that sites for activation of PLCbeta2, PLCbeta3, and adenylyl cyclase II overlap on the "top" surface of the propeller, where Galpha also binds (Li, Y., Sternweis, P. M., Charnecki, S., Smith, T. F., Gilman, A. G., Neer, E. J., and Kozasa, T. (1998) J. Biol. Chem. 273, 16265-16272). The present study was undertaken to identify the regions on the side of the torus that might be important for effector interactions. We made mutations in each of the outer beta strands of the G protein beta1 propeller, as well as mutations in the loops that connect the outer strands to the adjacent beta strands. Our results suggest that activation of PLCbeta2 involves residues in the outer strands of blades 2, 6, and 7 of the propeller. We tested three of the mutations that most severely affected PLCbeta2 activity against two forms of adenylyl cyclase (ACI and ACII). Both inhibition of ACI and activation of ACII were unaffected by these mutations, suggesting that if ACI and ACII contact the outer strands, the sites of contact are different from those for PLCbeta2. We propose that distinct sets of contacts along the sides of the propeller will define the specificity of the interaction of betagamma with effectors.

Adenylyl Cyclases

Regulation of adenylyl cyclase by membrane potential.

Mammalian adenylyl cyclases possess 12 transmembrane-spanning domains and bear a superficial resemblance to certain classes of ion channels. Some evidence suggests that bacterial and sea urchin sperm adenylyl cyclases can be regulated by membrane depolarization. In the present study, we explored the effect of altering membrane potential on the adenylyl cyclase activity of cerebellar granule cells with acute potassium depolarization. A biphasic stimulatory and then inhibitory response is evoked by progressive increases in the extracellular [K]:[Na] ratio in the absence of extracellular Ca2+. This effect does not mimic the linear increase in membrane potential elicited under the same conditions. Instead it appears as though membrane depolarization opens L-type (nimodipine-sensitive) Ca2+ channels, allowing the entry of Na+, which directly stimulates adenylyl cyclase activity. Gramicidin, which generates pores that are permeable to monovalent cations, and concurrently eliminates the membrane potential, permits a similar stimulation by extracellularly applied Na+. Although the results indicate no direct sensitivity of cerebellar granule cell adenylyl cyclase to membrane potential, they do demonstrate that, as a result of membrane depolarization, the influx of Na+, as well as Ca2+, will elevate cAMP levels.

Adenylyl Cyclases