title: Effects of dopamine on voltage-dependent potassium currents in identified rat lactotroph cells.
abstract: The effects of dopamine (DA) on voltage-dependent potassium currents were investigated in rat lactotrophs maintained in primary culture. Lactotroph cells were identified using the reverse hemolytic plaque assay. Membrane currents and potentials of lactotroph cells were recorded using the patch-clamp recording technique in the 'whole-cell' configuration. In the presence of cobalt (2 mM), two types of voltage-dependent K+ currents were recorded, a voltage-activated delayed K+ current (IK) and a voltage-activated transient K+ current (IA). The current IK was activated at membrane potentials varying from -20 to +40 mV and did not inactivate during prolonged voltage steps (up to 25 s); it was blocked by tetraethylammonium (10 mM). The current IA was activated at membrane potentials higher than -45 mV and showed a voltage-dependent inactivation between -110 and -40 mV; it was slightly inhibited by 4-aminopyridine (5 mM). Under current-clamp conditions, the majority of the cells (60%) showed spontaneous Ca2(+)-dependent action potentials (APs) while silent cells (40%) were excitable by depolarizing current pulses. Bath application of 10 nM DA evoked a hyperpolarizing response, blocked spontaneous APs and decrease the amplitude of evoked APs. Only the hyperpolarizing response faded during the course of the whole cell recording experiments. Under voltage-clamp conditions, DA induced a reversible increase in both voltage-dependent outward K+ currents, without modifying their thresholds. Steady-state inactivation of IA was not affected by DA. These DA-induced responses were dose-dependent and they involved D2 receptor activation. They were mimicked by the specific D2 receptor agonist bromocriptine (10 nM) and blocked by the specific D2 receptor antagonist sulpiride (100 nM), the D1 antagonist SCH 23390 being ineffective. The ability of DA to increase voltage-dependent K+ currents cannot be observed without GTP in the recording pipette. It was pertussis-toxin-sensitive but was affected neither by bath application of 1 mM forskolin nor by the presence of 500 microM cyclic AMP with 500 microM 3-isobutyl-1-methylxanthine in the pipette solutions. We conclude that in lactotroph cells DA specifically increases two voltage-dependent K+ currents via a pertussis-toxin-sensitive guanine nucleotide regulatory protein and appears to be independent of intracellular cyclic AMP. This effect leads to a decrease in the excitability of the cell, explaining in part the inhibitory effect of DA on prolactin release.
authors: Inserm U.176, Bordeaux, France.
authors: P M
authors: PM
authors: Lledo
authors: P
authors: P
authors: Legendre
authors: J
authors: J
authors: Zhang
authors: J M
authors: JM
authors: Israel
authors: J D
authors: JD
authors: Vincent
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004553:Electric Conductivity; D005260:Female; D007700:Kinetics; D008564:Membrane Potentials; D037342:Pertussis Toxin; D010902:Pituitary Gland / Q000166:cytology / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D015221:Potassium Channels; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013757:Tetraethylammonium Compounds; D010566:Virulence Factors, Bordetella; D001971:Bromocriptine; D003035:Cobalt; D019789:Tetraethylammonium; D013469:Sulpiride; D011388:Prolactin; D015761:4-Aminopyridine; D037342:Pertussis Toxin; D002118:Calcium; D004298:Dopamine