Potassium channels involved in the transduction mechanism of dopamine D2 receptors in rat lactotrophs
1. Radioactive rubidium (86Rb+) efflux was used to measure potassium (K+) permeability in a study designed to asses both the presence and the sensitivity to ions and drugs of the K+ channels in the plasma membrane of rat lactotrophs. 2. Rb+ efflux from Rb+-pre-loaded lactotrophs into nominally calci...
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Published in | The Journal of physiology Vol. 410; no. 1; pp. 251 - 265 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
The Physiological Society
01.03.1989
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Subjects | |
Online Access | Get full text |
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Summary: | 1. Radioactive rubidium (86Rb+) efflux was used to measure potassium (K+) permeability in a study designed to asses both the
presence and the sensitivity to ions and drugs of the K+ channels in the plasma membrane of rat lactotrophs. 2. Rb+ efflux
from Rb+-pre-loaded lactotrophs into nominally calcium-free solution containing 5 mM-K+ was linear from 1 to 60 s, with a
calculated rate of about 0.1%/s. Raising K+ concentrations to depolarize the cells stimulated the Rb+ efflux (0.2%/s), which
was already significant after 1 s of exposure of the cell to 100 mM-K+. This component of Rb+ efflux has been designated component
V (sensitive to voltage and Ca2+ independent). 3. Addition of Ca2+ to 5 mM-K+ solution had no effect on resting Rb+ efflux
(0.1%/s), but did further stimulate Rb+ efflux into K+-rich solutions. This component, which has been designated component
C, was completely inhibited by 0.5 mM-cadmium. These data fit the view that the increase in intracellular Ca2+ concentration
during depolarization opens certain (Ca2+-activated) K+ channels. 4. K+ efflux was differently affected by K+ channel blockers.
Tetraethylammonium (TEA) inhibited both V and C components while 4-aminopyridine (4-AP) inhibited the component V without
modifying the C component of Rb+ efflux. 5. Dopamine appears to affect both types of Rb+ efflux components. Dopamine increased
the efflux of Rb+ in a nominally Ca2+-free medium containing 5 mM-K+ (component V). This effect was statistically significant
15 s after exposure of the cells to 10 nM-dopamine. Increasing the concentrations of K+ to gradually depolarize the cells
enhanced the rate of increase of Rb+ efflux induced by dopamine, being evident in the initial 2-5 s of incubations. Dopamine
also increased Rb+ efflux in a 5 mM-K+ solution containing 1 mM-Ca2+ (component C). This effect was rapid (2-5 s) and inhibited
by 0.5 mM-cadmium. The combined action of dopamine on both component C and V caused the cells to be less sensitive to depolarizing
concentrations of K+. The increase in Rb+ efflux and the enhancement of prolactin release induced by high concentrations of
K+ were, indeed, prevented by exposure of the cells to 10 nM-dopamine. 6. The effects of dopamine on either component V or
component C were pharmacologically characterized as D2 receptor mediated, being mimicked by selective D2 receptor agonists
(quinpirole and RU 24213) and stereospecifically blocked by the D2 receptor antagonist sulpiride. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/jphysiol.1989.sp017531 |