Potassium channels involved in the transduction mechanism of dopamine D2 receptors in rat lactotrophs

• Published in: The Journal of physiology Vol. 410; no. 1; pp. 251 - 265
• Main Authors: Castelletti, L, Memo, M, Missale, C, Spano, P F, Valerio, A
• Format: Journal Article
• Language: English
• Published: England The Physiological Society 01.03.1989
• Subjects: 4-Aminopyridine - pharmacology; Animals; Cadmium - pharmacology; Colforsin - pharmacology; Cyclic AMP - pharmacology; Dopamine - pharmacology; Female; Kinetics; Pituitary Gland, Anterior - metabolism; Potassium Channels - drug effects; Potassium Channels - metabolism; Rats; Rats, Inbred Strains; Receptors, Dopamine - metabolism; Receptors, Dopamine D2; Rubidium Radioisotopes - metabolism
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.1989.sp017531

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.