Dopamine D2 receptor activation depolarizes rat supraoptic neurones in hypothalamic explants.
1. Intracellular current and voltage clamp recordings were obtained from rat supraoptic nucleus neurones in superfused hypothalamic explants in order to evaluate their response to dopamine and to D1 and D2 agonists. 2. With one exception, exposure to dopamine (10-200 microM) depolarized supraoptic neurones. When tested for an effect on twenty-one spontaneously active supraoptic neurones, dopamine enhanced the firing of all eleven continuous-firing (possibly oxytocin-secreting) neurones and prolonged the burst in all ten phasic-firing (vasopressin-secreting) neurones. 3. In sixty-seven of sixty-eight neurones where current injection was used to maintain membrane potential below threshold for action potential generation, current clamp data revealed that exposure to dopamine (10-200 microM) was followed in 10-17 s by a gradual 3-7 mV membrane depolarization that lasted for 4-15 min and was accompanied by a 12-23% reduction in input resistance. Exposure to quinpirole, a D2 agonist (10-200 microM), induced a similar response with comparable onset, duration and change in input resistance. In contrast, tests on sixteen cells indicated little or no response to a D1 agonist SKF38393. 4. Under voltage clamp, dopamine was noted to induce an inward current, accompanied by a 7.5-40% increase in membrane conductance over the corresponding time course. 5. Voltage-current plots for dopamine-induced depolarizations were linear in the range -50 to -110 mV. Dopamine and quinpirole depolarizations had extrapolated mean reversal potentials of -25 +/- 10 mV (mean +/- S.D.) and -20 +/- 15 mV respectively. This approximated the mean reversal potential of -20 +/- 8 mV measured from the dopamine-induced inward current using single-electrode voltage clamp. 6. The actions of dopamine were selectively antagonized by two D2 receptor antagonists, sulpiride and spiperone, but neither influenced membrane depolarizations induced by equimolar concentrations of noradrenaline. Dopamine-induced depolarizations also persisted following selective blockade of alpha 1-adrenergic receptors by prazosin; under these conditions, noradrenaline induced membrane hyperpolarization. 7. Following complete substitution of external Na+ with Tris, the reversal potential for the dopamine-induced response was shifted to -70 +/- 9.8 mV. This value was consistently less negative than the estimated potassium equilibrium potential. 8. The depolarization action of dopamine persisted in media containing tetrodotoxin and with an external calcium concentration ([Ca2+]o) of 0 mM-Ca2+ with 6 mM-Mg2+ or Mn2+, but was abolished following intracellular injection of [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a Ca2+ chelator.(ABSTRACT TRUNCATED AT 400 WORDS)
Division of Neurology, Ottawa Civic Hospital, Ontario, Canada.
C R
CR
Yang
C W
CW
Bourque
L P
LP
Renaud
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology*; D019257:Quinpirole; D051381:Rats; D011954:Receptors, Dopamine / Q000502:physiology*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000502:physiology*
D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D013134:Spiperone; D013469:Sulpiride; D002118:Calcium; D004298:Dopamine